Original Article
Expression of Blood-Group Antigen A — A Favorable Prognostic Factor in Non-Small-Cell Lung Cancer
N Engl J Med 1991; 324:1084-1090April 18, 1991
- Abstract
- Abstract
Background.
New prognostic factors are needed to guide the treatment of patients with non-small-cell lung cancer. We evaluated the prognostic value of altered expression of ABH blood-group antigens, which has been implicated in the multistep process of carcinogenesis and tumor progression.
Methods.
The presence of blood-group antigens was assessed immunohistochemically in paraffin-embedded tumor samples from 164 patients who underwent curative surgery for non-small-cell lung cancer from 1980 through 1982. Monoclonal antibodies were used to detect the A and B antigens, and Ulex europaeus agglutinin I to detect H antigen.
Results.
Survival of the 28 patients with blood type A or AB who had primary tumors negative for blood-group antigen A was significantly shorter than that of the 43 patients with antigen A—positive tumors (P<0.001) and of the 93 patients with blood type B or O (P = 0.002). The respective median survival times were 15, 71, and 39 months. Disease progressed significantly earlier in the 28 patients with tumors negative for blood-group antigen A than in the antigen A—positive patients (P<0.001). Expression of blood-group antigen B or H in tumor cells did not correlate with survival. Cox proportional-hazards regression analysis showed that expression of blood-group antigen A in tumor cells added significantly to the prediction of overall survival provided by other known prognostic factors among the patients with blood type A or AB (P = 0.004).
Conclusions.
Expression of blood-group antigen A in tumor cells is an important favorable prognostic factor in patients with non-small-cell lung cancer. This variable needs to be considered in the design of future trials of therapy. (N Engl J Med 1991; 324:1084–90.)
Media in This Article
Figure 1
Adenocarcinoma of the Lung from a Patient with Type AB Blood after Staining with Hematoxylin and Eosin (Panel A), Anti-EGFR Antibody 29.1 (Positive, Panel B), Anti-A Antibody (Positive, Panel C), and Anti-B Antibody (Negative, Panel D) (Original Magnification, ×l00).Figure 2
Kaplan–Meier Estimation of Overall Survival for All Patients, According to Antigen A Status in Tumor Cells.Article Activity
- Article
IN patients with non-small-cell lung cancer, the most important prognostic factor is tumor stage, and this factor largely determines treatment.1 , 2 Surgery is the standard mode of treatment for patients with stage I and II tumors and for some patients with stage III tumors, with postoperative radiation therapy or chemotherapy (or both) added if the tumor invades the mediastinal lymph nodes. Even after apparently complete resection, however, five-year survival is still no more than 40 percent,2 and the factors that account for disparate outcomes within the same stage are mostly unknown.
Recently, in examining the expression of epidermal growth factor receptor (EGFR) in paraffin-embedded samples of tissue with non-small-cell lung cancer, we found that immunostaining with the anti-EGFR monoclonal antibody3 29.1 was associated with a favorable clinical outcome after surgical resection.4 Because this antibody has been found to cross-react with an epitope for blood-group antigen A,5 we expanded our study to determine whether the expression of blood-group antigens in tumor cells has the same prognostic importance in this disease.
ABH blood-group antigens are found in a variety of epithelial cells, as well as in erythrocytes; the antigenic determinants are carbohydrate side chains of glycoproteins and glycolipids. The expression of ABH blood-group antigens in relation to cancer development and cellular differentiation and maturation has been a subject of renewed interest.6 , 7 Since the expression of blood-group antigens in tissue depends on blood type, we studied the survival of patients within the context of their ABO blood type. Our results indicate that expression of blood-group antigen A in tumor cells, but not of blood-group antigens B or H, is an important prognostic factor in patients with non-small-cell lung cancer who undergo surgery.
Methods
Patients
Our initial review included 253 patients who underwent surgery for lung cancer at the University of Texas M.D. Anderson Cancer Center from January 1980 through December 1982. This closing date provided a minimal follow-up period of 60 months for patients not lost to follow-up. We reviewed the medical records, original pathology reports, and histologic slides to identify patients with pathologically confirmed non-small-cell lung cancer of postsurgical pathological stages I to IIIb.1 Clinical data, including ABO blood type as determined by the blood bank before surgery, were obtained from the medical records. The criteria for exclusion from the study were preoperative chemotherapy or radiotherapy, death within one month after surgery, and any intercurrent cancer. For 164 of the 175 patients who met the criteria for inclusion, tumor samples were available for immunostaining, and these samples were the focus of this study.
Histopathological Examination
All the histologic sections were reviewed by two of us. The histologic type of the tumor was determined in accordance with the criteria of the World Health Organization.8 The other histologic measures assessed were the nuclear grade,9 number of mitoses per 10 high-power fields, presence or absence of lymph-node metastasis, presence or absence of vascular invasion, and presence or absence of tumor in the margins of the resected tissue.
Immunohistochemical Staining
For the immunohistochemical studies, paraffin-embedded tumor samples were selected to correspond with representative samples of the primary tumor. Samples of regional lymph nodes containing metastases were also retrieved, when available, for comparative study. Five-micrometer sections were deparaffinized with xylene and ethanol. Intrinsic peroxidase activity in tissue was blocked by treatment for five minutes with 3 percent hydrogen peroxide in methanol. Immunolocalization was carried out with the avidin–biotin–peroxidase enzyme complex Elite kit (Vector Laboratories, Burlingame, Calif.), according to the manufacturer's directions.
Staining in a section of tumor was considered positive if unequivocal staining of membranes or cytoplasm was seen in more than 5 percent of the tumor cells. When staining was confined to the nucleus, the section was considered negative. Erythrocytes and vascular endothelium in the same section were used as internal positive controls, and lymphocytes and fibroblasts as internal negative controls.
Monoclonal Antibodies
Mouse monoclonal antibodies to blood-group antigens A and B (Ortho Diagnostic Systems, Raritan, N.J.) were used in 1:10 dilution. Biotinylated Ulex europaeus agglutinin I (UEA-I; Vector Laboratories) was used in 1:100 dilution to detect the blood-group H antigen.
Statistical Analysis
The Pearson chi-square test was used for contingency-table analyses.10 Life-table probabilities of overall survival (i.e., survival without regard to cause of death) were calculated by the method of Kaplan and Meier,11 and differences in survival between subgroups of patients were compared with the log-rank test.12 Overall length of survival was measured from the day of surgery. In the analysis of time to tumor progression, patients who died of unknown causes were considered to have had tumor progression. A Cox proportional-hazards regression model13 was used to determine the joint effect of several variables on survival.
Results
Characteristics of Patients
No significant differences in clinical or pathological characteristics at the time of surgery were found when the patients were grouped according to blood type (Table 1Table 1
Characteristics of the Patients According to Blood Type.). A higher percentage of patients with type AB blood had lymph-node involvement. The distribution of blood types was not different from that in the general population.14 Staining of Primary Tumor with Anti-A Antibody
Forty-three of the 164 primary tumors stained positive with the anti-A antibody, all from patients with type A or AB blood. The staining pattern indicated that the antigen was found in both the cytoplasm and membranes (Fig. 1Figure 1
Adenocarcinoma of the Lung from a Patient with Type AB Blood after Staining with Hematoxylin and Eosin (Panel A), Anti-EGFR Antibody 29.1 (Positive, Panel B), Anti-A Antibody (Positive, Panel C), and Anti-B Antibody (Negative, Panel D) (Original Magnification, ×l00).). There was no aberrant expression of blood-group antigen A in the tumor cells from the patients with type B or type O blood.Expression of Blood-Group Antigen A in Metastatic Tumors
Expression of blood-group antigen A was also assessed in metastatic tumors in regional lymph nodes from 27 patients with blood of type A or AB. Among 16 patients whose primary tumor stained positive with anti-A antibody, 4 patients had metastases that did not stain with the anti-A antibody. Among 11 patients whose primary tumor was negative for antigen A expression, none had metastases that stained with anti-A antibody.
Staining of Primary Tumor for Blood-Group Antigens B and H
Staining with the anti-B antibody was positive in the tumors from 8 of the 30 patients with blood type B or AB, and the tumors from 42 of the 73 patients with blood type O stained positive with UEA-I (anti-H). Among the patients with blood type AB, expression of antigen A was unrelated to that of antigen B, as shown in Figure 1.
Survival According to Expression of Blood-Group Antigens
At the most recent follow-up, 61 patients were alive (median follow-up, 76 months; range, 2 to 105), and 103 were dead (median time to death, 20 months; range, 2 to 85). Since the expression of blood-group antigen A in tumor cells was confined to patients with type A or AB blood, the survival analysis according to expression of blood-group antigen A was stratified into blood groups A and AB, on the one hand, and groups B and O, on the other.
For the 28 patients with type A or AB blood who had primary tumors negative for blood-group antigen A, the median survival was 15 months. In contrast, the median survival was 71 months in the 43 patients with blood type A or AB who had expression of antigen A in their tumor cells (P<0.001). The estimated three- and five-year survival rates were 22 and 15 percent, respectively, for the patients negative for blood-group antigen A and 74 and 59 percent for the antigen A—positive group. In comparison, the median survival of the 93 patients with type B or O blood was 39 months, with three- and five-year survival rates of 51 and 38 percent, respectively (Fig. 2Figure 2
Kaplan–Meier Estimation of Overall Survival for All Patients, According to Antigen A Status in Tumor Cells.). The difference in survival between the patients with type A or AB blood whose tumors were negative for blood-group antigen A and those with type B or O blood was significant (P = 0.002), as was the difference in survival between the patients with type A or AB blood whose tumors were positive for antigen A and those with type B or O blood (P = 0.033).In contrast, the loss of blood-group antigen B or H in tumor cells was not associated with a disadvantage for survival either in the patients with type B or AB blood (P = 0.826) or in those with type O blood (P = 0.912).
Independent Predictive Value of Expression of Blood-Group Antigen A
Tumors negative for blood-group antigen A were significantly more likely than those positive for antigen A to have a high mitotic rate (P = 0.001), to be large (P = 0.036) and less differentiated (P = 0.026), and to be composed of large-cell carcinomas (P = 0.055) (Table 2Table 2
Outcome in Patients with Blood Type A or AB, According to Positivity or Negativity for Blood-Group Antigen A in Tumor Cells and Clinicopathological Characteristics.). There was no correlation between antigen A status and age, sex (data not shown), tumor stage, nodal status, presence or absence of vascular invasion (data not shown), or nuclear grade (data not shown).When overall survival rates were compared by a log-rank test, the lack of expression of blood-group antigen A in tumor cells was associated with a worse prognosis among the patients with adenocarcinoma (P<0.001) and those with squamous-cell carcinoma (P<0.001), and in tumors of either size category (Table 2). In the eight patients with large-cell carcinoma, the length of survival was indistinguishable from that in the patients with adenocarcinoma or squamous-cell carcinoma that was negative for blood-group antigen A.
Of particular interest was the examination of whether status with respect to the expression of blood-group antigen A added predictive value to tumor stage, the most widely used prognostic factor in non-small-cell lung cancer. Among the patients with type A or AB blood who had stage I disease, survival in those with tumors negative for blood-group antigen A was far shorter (Fig. 3AFigure 3
Kaplan–Meier Estimation of Overall Survival According to Positive or Negative Antigen A Status in Tumor Cells and Disease Stage in Patients with Type A or AB Blood.); the median survival was only 19 months. For the patients with tumors positive for antigen A, however, the median survival was not reached at the end of the study; their five-year survival rate was 76.5 percent (P<0.001). Even among the patients with stage II disease, survival in those with tumors negative for blood-group antigen A was shorter than in the patients with tumors positive for antigen A (P = 0.048), with a median survival of 11 months as compared with 53 months (Fig. 3B). In the patients with stage III disease, there was a trend toward the same survival advantage with tumors that expressed blood-group antigen A, but statistical significance was not reached (P = 0.158), perhaps because of the small sample (Fig. 3C).Joint Effects of Variables
Whether tumor expression of blood-group antigen A added significantly to the information provided by the other variables was explored with use of parsimonious models obtained by a backward-elimination procedure. Among the patients with type A or AB blood, univariate analysis demonstrated that age (P = 0.023), nodal status (P = 0.008), and mitotic rate (P = 0.072) were of significant prognostic value and that tumor-cell type, stage, tumor size, vascular invasion, degree of differentiation, and resection-margin status were not (P>0.22; maximal relative hazard for these variables, 1.82).
Removing age from the model that included age, nodal status, and mitotic rate did not render the model significantly worse according to the log-likelihood criterion (P = 0.144). After age was removed, however, neither nodal status nor mitotic rate could be eliminated at a 0.05 level of significance. This model was significantly improved by the addition of blood-group antigen A status in tumor cells (P = 0.004); that is, antigenic status added predictive value to that achieved with the other prognostic factors. However, although removing mitotic rate from the model including mitotic rate, nodal status, and antigenic status did not render the model significantly worse (P = 0.238), neither of the remaining two prognostic factors could be dropped.
When the proportional-hazards model for survival was fitted to the six groups obtained from the model (two groups for antigen A status times three groups for nodal status), we found three homogeneous risk groups. The low-risk group consisted of the 23 patients (32 percent) who had no nodal disease but had expression of blood-group antigen A in their tumor; we arbitrarily assigned this group a relative hazard of 1.0. The intermediate-risk group included the 10 patients (14 percent) with Nl staging and tumors positive for blood-group antigen A; their relative hazard was 3.47. The remaining 38 patients (54 percent) were at high risk of death, with relative hazards ranging from 7.24 to 8.59; that is, all the patients with tumors negative for blood-group antigen A were at increased risk, regardless of nodal status, as were all the patients with N2 disease, regardless of antigen A status.
Patterns of Disease Progression
To understand better the pathobiologic implications of the expression of blood-group antigen A in non-small-cell lung cancer, we analyzed the pattern of disease progression. Progressive disease, taken to include second primary tumors, occurred in 17 of the 43 patients with tumors positive for blood-group antigen A in tumor cells (Table 3Table 3
Patterns of Initial Progression of Disease, According to Antigen A Status in Tumor Cells in Patients with Type A or AB Blood.) after a median of 18 months (range, 2 to 83); in 14 of the 28 patients negative for blood-group antigen A who had type A or AB blood, progression occurred after a median of 6 months (range, 2 to 16). The difference between the times to progression of disease was significant (P<0.001) according to life-table analysis. The 43 patients with tumors positive for blood-group antigen A also had a significantly longer time to progression of disease than the 93 patients with type B or O blood (P = 0.026).Distant metastasis was the most frequent type of tumor spread; its rate was higher in the patients negative for blood-group antigen A than in the antigen A—positive patients (12 of 28 vs. 10 of 43; P = 0.082). The brain was a common site of disease spread, but there was no difference with respect to blood-group antigen A status. However, the patients negative for antigen A had bone metastasis more often than those positive for antigen A (5 of 28 vs. 1 of 43; P = 0.033).
Discussion
We found that expression of blood-group antigen A in tumor cells is an important favorable prognostic factor for overall survival and the time to progression of disease in patients with non-small-cell lung cancer. Most important, perhaps, are the findings in the patients with stage I disease, in whom the loss of expression of blood-group antigen A in tumor cells was associated with shorter survival, of a length not significantly different from that in the patients with stage II or III disease (Fig. 3). In addition, the retention of expression of blood-group antigen A in tumor cells conferred an improved prognosis, and the loss of such expression conferred a worsened prognosis for survival than that of the patients with type B or O blood. For the patients with type B or O blood, however, the expression of blood-group antigen B or H in tumor cells did not correlate with survival, suggesting that the important variable is something other than the simple retention or loss of blood-group antigen.
The data reported here suggest that loss of expression of blood-group antigen A is a possible marker for the multistage process of tumor progression in patients with type A or AB blood. First, expression of this antigen was lost more often in larger tumors (>3 cm) than in smaller ones. Second, expression of blood-group antigen A was lost more frequently in metastatic lesions in lymph nodes than in primary tumors. Third, loss of expression of the antigen was associated with a shorter time to the progression of disease. Along with this evidence, some other clinicopathological features (i.e., large-cell histology and bony metastasis) that were associated with the loss of expression of blood-group antigen A in our study have been previously found to predict decreased survival in patients with recurrent or metastatic non-small-cell lung cancer.15
Altered expression of ABH blood-group antigens during malignant transformation and tumor progression has been previously reported.16 17 18 19 In addition, loss of expression of blood-group A and B antigens occurs during wound healing.20 , 21 For example, within hours after a wound, expression of blood-group antigen is lost from the epithelial cells adjacent to the wound margin, as well as from the epithelial cells migrating into the wound. Antigenic expression returns to normal after the restoration of epithelial continuity.21 These findings are intriguing in the light of our finding that a loss of expression of blood-group antigen A appears to be closely related to the risk of metastasis. Indeed, it has been suggested that the loss of expression of blood-group ABH or Lea antigen is associated with more aggressive tumor behavior in cancers of the bladder,22 23 24 25 26 uterine cervix,16 , 27 colon,28 and head and neck.29
In lung cancers, using a specific red-cell-adherence technique, Davidsohn and Ni30 found expression of ABH antigens in only 5 of 18 adenocarcinomas, in none of 86 other primary bronchogenic carcinomas, and in none of 145 metastases. When Hirohashi et al.31 used an immunohistochemical technique (which is more sensitive than the specific red-cell-adherence technique), they detected appropriate expression of blood-group antigens in 34 of 42 adenocarcinomas of the lung. Most of these clinical studies, however, failed to show a specific association of expression of blood-group antigen A with improved clinical outcome, a result perhaps attributable to the lack of stratification according to blood group or, in some series, to an insufficient number of patients studied.24 , 29
These results suggest that expression of ABH blood-group antigens might be used to stratify patients in future clinical trials designed to evaluate the efficacy of postoperative adjuvant chemotherapy, particularly for patients with type A or AB blood. Given their relatively poor prognosis after surgery, such patients who have primary non-small-cell lung cancers that are negative for blood-group antigen A seem to merit aggressive and innovative treatment approaches, even those with early-stage tumors. If the primary tumor is found to be negative for blood-group antigen A before surgery, for example, primary induction chemotherapy and radiation therapy might be considered as an alternative to immediate surgery —an approach similar to that used in patients with advanced laryngeal cancer to preserve the natural voice.32
Supported in part by grants (CA-45746 and CA-11672) from the National Institutes of Health.
We are indebted to Ms. Monica Lotay and Ms. Susan Cweren for their excellent technical help, to Ms. Cynthia Waters and Ms. Terry Saulsberry for assistance in the preparation of the manuscript, to Ms. Suzanne Simpson for editorial review, and to the Department of Patient Studies for providing lists of patients.
Source Information
From the Departments of Medical Oncology (J.S.L., W.K.H., W.N.H.), Pathology (J.Y.R., A.A.S.), Biomathematics (B.W.B.), and Thoracic Surgery (C.F.M.), the University of Texas M.D. Anderson Cancer Center, Houston. Address reprint requests to Dr. Lee at the Department of Medical Oncology, Box 80, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
- References
References
1
Mountain
Web of Science | Medline2
Naruke
Web of Science | MedlineErratum, J Thorac Cardiovasc Surg 1989; 97:350.
Web of Science3
Yarden
Web of Science | Medline4
Lee 5
Gooi
CrossRef | Web of Science | Medline6
Hakomori
CrossRef | Web of Science | Medline7
Clausen
CrossRef | Web of Science | Medline8
The World Health Organization histological typing of lung tumours . 2nd ed. Am J Clin Pathol 1982; 77:123–36.
Web of Science | Medline9
Black
Web of Science | Medline10
Snedecor GW, Cochran WG. Statistical methods. 6th ed. Ames: Iowa State University Press, 1967.
11
Kaplan
CrossRef | Web of Science12
Mantel
Medline13
Cox 14
Giblett ER. Erythrocyte antigens and antibodies. In: Williams WJ, Beutler E, Erslev AJ, Lichtman MA, eds. Hematology. 3rd ed. New York: McGraw-Hill, 1983:1491–505.
15
Finkelstein
Web of Science | Medline16
Davidsohn
Web of Science | Medline17
Dabelsteen
Medline18
Dabelsteen
CrossRef | Web of Science | Medline19
Ørntoft
CrossRef | Web of Science | Medline20
Dabelsteen
Medline21
Mackenzie 22
Kay
Web of Science | Medline23
Fujioka
CrossRef | Web of Science | Medline24
Juhl
CrossRef | Web of Science | MedlineErratum, Cancer 1986; 58:1184.
CrossRef | Web of Science25
Summers
Web of Science | Medline26
Limas
CrossRef | Web of Science | Medline27
Davidsohn
Web of Science | Medline28
Schoentag
CrossRef | Web of Science | Medline29
Carey
Web of Science | Medline30
Davidsohn
Web of Science | Medline31
Hirohashi
Web of Science | Medline32
Hong
- Citing Articles (67)
Citing Articles
1
Pablo León-Atance, Nicolás Moreno-Mata, Federico González-Aragoneses, Miguel Ángel Cañizares-Carretero, Enrique Poblet-Martínez, Marta Genovés-Crespo, María Dolores García-Jiménez, Antonio Francisco Honguero-Martínez, Carlos Alberto Rombolá, Carlos María Simón-Adiego, Rafael Peñalver-Pacual, Emilio Álvarez-Fernández. (2012) Prognostic Influence of Loss of Blood Group A Antigen Expression in Pathologic Stage I Non-Small-Cell Lung Cancer. Archivos de Bronconeumología (English Edition)
CrossRef2
Peter Arend. (2011) “Natural” antibodies and histo-blood groups in biological development with respect to histo-blood group A. A perspective review. Immunobiology 216:12, 1318-1321
CrossRef3
Pablo León-Atance, Nicolás Moreno-Mata, Federico González-Aragoneses, Miguel Ángel Cañizares-Carretero, Enrique Poblet-Martínez, Marta Genovés-Crespo, María Dolores García-Jiménez, Antonio Francisco Honguero-Martínez, Carlos Alberto Rombolá, Carlos María Simón-Adiego, Rafael Peñalver-Pacual, Emilio Álvarez-Fernández. (2011) Influencia pronóstica de la pérdida de la expresión del antígeno del grupo sanguíneo A en el carcinoma no microcítico de pulmón en estadio I patológico. Archivos de Bronconeumología
CrossRef4
Qiwen Ben, Kaixuan Wang, Yaozong Yuan, Zhaoshen Li. (2011) Pancreatic cancer incidence and outcome in relation to ABO blood groups among Han Chinese patients: A case-control study. International Journal of Cancer 128:5, 1179-1186
CrossRef5
Miao-Zhen Qiu, Dong-Sheng Zhang, Dan-Yun Ruan, Hui-Yan Luo, Zhi-Qiang Wang, Zhi-Wei Zhou, Feng-Hua Wang, Yu-Hong Li, Rui-Hua Xu. (2010) A relationship between ABO blood groups and clinicopathologic characteristics of patients with gastric adenocarcinoma in China. Medical Oncology
CrossRef6
Stephen L. Graziano, Lin Gu, Xiaofei Wang, Arthur H. Tatum, Robin T. Vollmer, Gary M. Strauss, Robert Kratzke, Arkadiusz Z. Dudek, Everett E. Vokes, Mark R. Green. (2010) Prognostic Significance of Mucin and p53 Expression in Stage IB Non-small Cell Lung Cancer. Journal of Thoracic Oncology 5:6, 810-817
CrossRef7
B. M. Wolpin, P. Kraft, C. S. Fuchs. (2010) Response: Re: ABO Blood Group and the Risk of Pancreatic Cancer. JNCI Journal of the National Cancer Institute 102:2, 137-137
CrossRef8
Shin-Yi Yu, Zhangung Yang, Kay-Hooi Khoo, Albert M. Wu. (2009) Identification of blood group A/A-Le b/y and B/B-Le b/y active glycotopes co-expressed on the O-glycans isolated from two distinct human ovarian cyst fluids. PROTEOMICS 9:13, 3445-3462
CrossRef9
Sen-itiroh Hakomori. (2008) Structure and function of glycosphingolipids and sphingolipids: Recollections and future trends. Biochimica et Biophysica Acta (BBA) - General Subjects 1780:3, 325-346
CrossRef10
Kaori Tsuboi, Takayuki Asao, Munenori Ide, Shinji Hashimoto, Kasumi Noguchi, Yoshihiko Kominato, Abby R. Saniabadi, Hiroyuki Kuwano, Shin Yazawa. (2007) α1,2Fucosylation Is a Superior Predictor of Postoperative Prognosis for Colorectal Cancer Compared with Blood Group A, B, or Sialyl Lewis X Antigen Generated within Colorectal Tumor Tissues. Annals of Surgical Oncology 14:6, 1880-1889
CrossRef11
Judit Papay, Tibor Krenacs, Judit Moldvay, Eva Stelkovics, Jozsef Furak, Bela Molnar, Laszlo Kopper. (2007) Immunophenotypic Profiling of Nonsmall Cell Lung Cancer Progression Using the Tissue Microarray Approach. Applied Immunohistochemistry & Molecular Morphology 15:1, 19-30
CrossRef12
Yuh-Ching Twu, Chuang-Yi Hsieh, Lung-Chih Yu. (2006) Expression of the histo-blood group B gene predominates in AB-genotype cells. Transfusion 46:11, 1988-1996
CrossRef13
Yusuke Suzuki, Minoru Suzuki, Emi Ito, Hiroshi Ishii, Kouzou Miseki, Akemi Suzuki. (2005) Convenient and rapid analysis of linkage isomers of fucose-containing oligosaccharides by matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight mass spectrometry. Glycoconjugate Journal 22:7-9, 427-431
CrossRef14
Yoshihiko Kominato, Yukiko Hata, Kazuhiro Matsui, Hisao Takizawa, Jun-ichi Tsukada, Tamiko Nakajima, Yasushi Kaneko, Koichiro Kishi. (2004) Transcriptional regulation of the human ABO histo-blood group genes is dependent on the N box upstream of the proximal promoter. Transfusion 44:12, 1741-1749
CrossRef15
Godehard Friedel, Volker Steger, Thomas Kyriss, Jutta Zoller, Heikki Toomes. (2004) Prognosis in N2 NSCLC. Lung Cancer 45, S45-S53
CrossRef16
T. Nozoe, T. Ezaki, H. Baba, Y. Kakeji, Y. Maehara. (2004) Correlation of ABO blood group with clinicopathologic characteristics of patients with esophageal squamous cell carcinoma. Diseases of the Esophagus 17:2, 146-149
CrossRef17
Gianfranco Buccheri, Domenico Ferrigno. (2004) Prognostic factors. Hematology/Oncology Clinics of North America 18:1, 187-201
CrossRef18
D. J. Becker. (2003) Fucose: biosynthesis and biological function in mammals. Glycobiology 13:7, 41R-53
CrossRef19
Eiji Hosoi, Masao Hirose, Shuichi Hamano. (2003) Expression levels of H-type alpha(1,2)-fucosyltransferase gene and histo-blood group ABO gene corresponding to hematopoietic cell differentiation. Transfusion 43:1, 65-71
CrossRef20
Christine L Lau, Mary-Beth H Moore, Kelly R Brooks, Thomas A D'Amico, David H Harpole. (2002) Molecular staging of lung and esophageal cancer. Surgical Clinics of North America 82:3, 497-523
CrossRef21
Erik Dabelsteen. (2002) ABO blood group antigens in oral mucosa. What is new?. Journal of Oral Pathology & Medicine 31:2, 65-70
CrossRef22
Tohru Nakagoe, Kiyoyasu Fukushima, Atsushi Nanashima, Terumitsu Sawai, Takashi Tsuji, Masa-Aki Jibiki, Hiroyuki Yamaguchi, Toru Yasutake, Hiroyoshi Ayabe, Tatsuki Matuo, Yutaka Tagawa. (2001) Comparison of the expression of ABH/Lewis-related antigens in polypoid and non-polypoid growth types of colorectal carcinoma. Journal of Gastroenterology and Hepatology 16:2, 176-183
CrossRef23
JACQUES PENDU, SÉVERINE MARIONNEAU, ANNE CAILLEAU-THOMAS, JÉZABEL ROCHER, BÉATRICE MOULLAC-VAIDYE, MONIQUE CLÉMENT. (2001) ABH and Lewis histo-blood group antigens in cancer. APMIS 109:1, 9-26
CrossRef24
Lung-Chih Yu, Ching-Yi Chang, Yuh-Ching Twu, Marie Lin. (2000) Human Histo-blood Group ABO Glycosyltransferase Genes: Different Enhancer Structures with Different Transcriptional Activities. Biochemical and Biophysical Research Communications 273:2, 459-466
CrossRef25
Maria Rios, Celso Bianca. (2000) The role of blood group antigens in infectious diseases. Seminars in Hematology 37:2, 177-185
CrossRef26
I Brockhausen. (1999) Pathways of O-glycan biosynthesis in cancer cells. Biochimica et Biophysica Acta (BBA) - General Subjects 1473:1, 67-95
CrossRef27
Torben F. Orntoft, Else Marie Vestergaard. (1999) Clinical aspects of altered glycosylation of glycoproteins in cancer. Electrophoresis 20:2, 362-371
CrossRef28
Syed A Mehdi, Joan E Etzell, Nancy B Newman, Noel Weidner, Leslie J Kohman, Stephen L Graziano. (1998) Prognostic significance of Ki-67 immunostaining and symptoms in resected stage I and II non-small cell lung cancer1Supported by Veterans Affairs Research Service.1. Lung Cancer 20:2, 99-108
CrossRef29
Daisuke Ichikawa, Kazuko Handa, Sen-itiroh Hakomori. (1998) Histo-blood group A/B antigen deletion/ reductionvs. continuous expression in human tumor cells as correlated with their malignancy. International Journal of Cancer 76:2, 284-289
CrossRef30
David H. Johnson. (1997) Adjuvant chemotherapy for non-small cell lung cancer. Lung Cancer 17, S103-S110
CrossRef31
Gary M. Strauss. (1997) PROGNOSTIC MARKERS IN RESECTABLE NON–SMALL CELL LUNG CANCER. Hematology/Oncology Clinics of North America 11:3, 409-434
CrossRef32
Stephen L. Graziano. (1997) Non-small cell lung cancer: clinical value of new biological predictors. Lung Cancer 17, S37-S58
CrossRef33
VIBEKE RAVN SKOVLUND. (1997) ABH and related histo-blood group antigens in normal & malignant human endometrium in relation to genetic and hormonal factors. APMIS 105:S69, 5-33
CrossRef34
ERIK DABELSTEEN. (1996) REVIEW ARTICLE. CELL SURFACE CARBOHYDRATES AS PROGNOSTIC MARKERS IN HUMAN CARCINOMAS. The Journal of Pathology 179:4, 358-369
CrossRef35
Elizabeth Rosvold. (1996) Prognostic factors for patients with non-small cell lung cancer. Current Problems in Cancer 20:4, 272-279
CrossRef36
Mamoru Kyogashima, Makoto Inoue, Akira Seto, Jin-ichi Inokuchi. (1996) Glucosylceramide synthetase inhibitor, d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol exhibits a novel decarcinogenic activity against Shope carcinoma cells. Cancer Letters 101:1, 25-30
CrossRef37
Jon H Ritter, Carolyn M Dresler, Mark R Wick. (1995) Expression of bcl-2 protein in stage T1NOMO non-small cell lung carcinoma. Human Pathology 26:11, 1227-1232
CrossRef38
Chikara Ohyama, Seiichi Orikasa, Sadafumi Kawamura, Makoto Satoh, Seiichi Saito, Yasuo Fukushi, Steven B. Levery, Sen-Itiroh Hakomori. (1995) Galactosylgloboside expression in seminoma. Inverse correlation with metastatic potential. Cancer 76:6, 1043-1050
CrossRef39
Jonathan C. Nesbitt, Joe B. Putnam, Garrett L. Walsh, Jack A. Roth, Clifton F. Mountain. (1995) Survival in early-stage non-small cell lung cancer. The Annals of Thoracic Surgery 60:2, 466-472
CrossRef40
Carolyn M. Dresler, Jon H. Ritter, Mark R. Wick, Charles L. Roper, G. Alexander Patterson, Joel D. Cooper. (1995) Immunostains for blood group antigens lack prognostic significance in T1 lung carcinoma. The Annals of Thoracic Surgery 59:5, 1069-1073
CrossRef41
Giorgio Vittorio Sotti, Paolo Masiero, Ernesto Pozzi. (1995) Biological prognostic factors in non-small cell lung cancer. Lung Cancer 12, S13-S25
CrossRef42
Shigeharu Kurimoto, Nobuo Moriyama, Kuniaki Takata, Shiro Nozawa, Yoshio Aso, Hiroshi Hirano. (1995) Detection of a glycosphingolipid antigen in bladder cancer cells with monoclonal antibody MRG-1. The Histochemical Journal 27:3, 247-252
CrossRef43
Thomas W. Rice, Raymond R. Tubbs, Gerald A. Hoeltge, Thomas J. Kirby, David P. Meeker, Sharon V. Medendorp, Ronald M. Bukowski. (1995) Expression of blood group antigen A by stage I non-small cell lung carcinomas. The Annals of Thoracic Surgery 59:3, 568-572
CrossRef44
R. Feld, M. Borges, V. Giner, R. Ginsberg, P. Harper, J. Klastersky, L. Lacquet, M. Paesmans, D. Payne, R. Rossell, W. Sause, J.P. Sculier, E. Shaw, J.B. Sorensen, T. Splinter, R. Stahel, P. Bunn. (1994) Prognostic factors in non-small cell lung cancer. Lung Cancer 11, S19-S23
CrossRef45
Toshiaki Kawai, Minoru Suzuki, Suminori Kono, Nariyoshi Shinomiya, Makoto Rokutanda, Keigo Takagi, Toshiro Ogata, Seiichi Tamai. (1994) Proliferating cell nuclear antigen and Ki-67 in lung carcinoma. Correlation with DNA flow cytometric analysis. Cancer 74:9, 2468-2475
CrossRef46
Rolf A. Stahel. (1994) Antigens, receptors and dominant oncogenes and the prognosis of non-small cell lung cancer. Lung Cancer 11, S31-S38
CrossRef47
John L. Gwin, Andres J. P. Klein-Szanto, Shi-Yu Zhang, Pasha Agarwal, Andre Rogatko, Steven M. Keller. (1994) Loss of blood group antigen a in non-small cell lung cancer. Annals of Surgical Oncology 1:5, 423-427
CrossRef48
Jill M. Siegfried, Autumn L.Gaither Davis, Joseph R. Testa, Jay D. Hunt, Robert J. Keenan, Samuel A. Yousem, Pamela S. Ritter, Peter F. Person, Rodney J. Landreneau. (1994) Ability to culture resectable non-small cell lung carcinomas is correlated with recurrence. The Annals of Thoracic Surgery 58:3, 662-667
CrossRef49
Rolf A. Stahel. (1994) Biology of lung cancer. Lung Cancer 10, S59-S65
CrossRef50
Martin H. Huber, Waun Ki Hong. (1994) Biology and chemoprevention of head and neck cancer. Current Problems in Cancer 18:2, 86-140
CrossRef51
Halina LIS, Nathan SHARON. (1993) Protein glycosylation. Structural and functional aspects. European Journal of Biochemistry 218:1, 1-27
CrossRef52
Pezzella, FrancescoTurley, HelenKuzu, IsinzuTungekar, Mohammed FahimDunnill, Michael S.Pierce, Chris B.Harris, AdrianGatter, Kevin C.Mason, David Y.. (1993) bcl-2 Protein in Non-Small-Cell Lung Carcinoma. New England Journal of Medicine 329:10, 690-694
Full Text53
Toshiaki Kawai, Minoru Suzuki, Katsuichi Kase, Yuichi Ozeki. (1993) Expression of carbohydrate antigens in human pulmonary adenocarcinoma. Cancer 72:5, 1581-1587
CrossRef54
M.L.M. Anderson, D.A. Spandidos. (1993) Oncogenes and onco-suppressor genes in lung cancer. Respiratory Medicine 87:6, 413-420
CrossRef55
Hidehiko Matsumoto, Hisako Muramatsu, Tetsurou Shimotakahara, Masakazu Yanagi, Hiroo Nishijima, Nobuyuki Mitani, Kuniaki Baba, Takashi Muramatsu, Hisaaki Shimazu. (1993) Correlation of expression of ABH blood group carbohydrate antigens with metastatic potential in human lung carcinomas. Cancer 72:1, 75-81
CrossRef56
Jin S. Lee, Scott M. Lippman, Waun K. Hong, Jae Y. Ro, Reuben Lotan, Walter N. Hittelman. (1993) Biomarkers in aerodigestive tract chemoprevention trials. Lung Cancer 9:1-6, 361-367
CrossRef57
Gary Slater, Steven Itzkowitz, Sasan Azar, Arthur H. Aufses. (1993) Clinicopathologic correlations of ABO and rhesus blood type in colorectal cancer. Diseases of the Colon & Rectum 36:1, 5-7
CrossRef58
Latifa Ghandur-Mnaymneh, William A. Raub, Kasi S. Sridhar, Jorge Albores-Saavedra, Edwin Gould, R. C. Duncan. (1993) The Accuracy of the Histological Classification of Lung Carcinoma and Its Reproducibility: A Study of 75 Archival Cases of Adenosquamous Carcinoma. Cancer Investigation 11:6, 641-651
CrossRef59
Thomas E. Carey, Thankam S. Nair, Catherine Chern, Monica Liebert, H. Barton Grossman, Gregory T. Wolf, Carter Van Waes. (1993) Blood group antigens and integrins as biomarkers in head and neck cancer: Is aberrant tyrosine phosphorylation the cause of altered α6β4 integrin expression?. Journal of Cellular Biochemistry 53:S17F, 223-232
CrossRef60
Masahiko Hirota, Hiroshi Egami, Masatoshi Mogaki, Katherine Kazakoff, William G. Chaney, Parviz M. Pour. (1993) Relationship between blood group-A antigen expression and malignant potential in hamster pancreatic cancers. Teratogenesis, Carcinogenesis, and Mutagenesis 13:5, 217-224
CrossRef61
Miyake, Masayuki, Taki, Toshihiko, Hitomi, Shigeki, Hakomori, Sen-itiroh, . (1992) Correlation of Expression of H/LeY/LeB Antigens with Survival in Patients with Carcinoma of the Lung. New England Journal of Medicine 327:1, 14-18
Full Text62
Lee, Jin S., Hong, Waun K., . (1992) Prognostic Factors in Lung Cancer. New England Journal of Medicine 327:1, 47-48
Full Text63
Hidehiko Matsumoto, Hisako Muramatsu, Takashi Muramatsu, Hisaaki Shimazu. (1992) Carbohydrate profiles shown by a lectin and a monoclonal antibody correlate with metastatic potential and prognosis of human lung carcinomas. Cancer 69:8, 2084-2090
CrossRef64
Thomas W. Rademacher. (1992) Therapeutic challenges: does Glycobiology have a role?. Trends in Biotechnology 10, 227-230
CrossRef65
Steven E. Benner, Waun K. Hong, Scott M. Lippman, Jin S. Lee, Walter M. Hittelman. (1992) Intermediate biomarkers in upper aerodigestive tract and lung chemoprevention trials. Journal of Cellular Biochemistry 50:S16G, 33-38
CrossRef66
M.F. TUNGEKAR, K.C. GATTER, M.S. DUNNILL, D.Y. MASON. (1991) Ki-67 immunostaining and survival in operable lung cancer. Histopathology 19:6, 545-550
CrossRef67
Sen-itiroh Hakomori. (1991) Possible functions of tumor-associated carbohydrate antigens. Current Opinion in Immunology 3:5, 646-653
CrossRef
