Correspondence

bcl-2 Protein in Non-Small-Cell Lung Carcinoma

N Engl J Med 1994; 330:221January 20, 1994

Article

To the Editor:

The potential value of the expression of bcl-2 protein as a diagnostic tumor marker and prognostic indicator in non-small-cell lung carcinoma, as described by Pezzella et al. (Sept. 2 issue),1 may be severely limited. The fact that bcl-2 protein was expressed in only 20 percent of their total group of 122 patients and in only 12 percent of patients with adenocarcinoma indicates that this approach is not sensitive enough to be of practical use as a diagnostic screening marker for early lung cancer. Furthermore, the low rate of bcl-2 expression also suggests that this marker is unlikely to be useful in conjunction with currently available tumor markers for lung cancer, which are also unable reliably to identify patients with early cancer2,3.

The authors' data show an inverse relation between increasing T and N stages and the likelihood of the expression of bcl-2. This would prevent the use of this protein marker in the initial clinical staging or restaging of non-small-cell lung carcinoma, since there is apparently no direct correlation between tumor burden and quantitative measurement of the protein.

The authors failed to mention the sites of tumor recurrence, although the greatest value of a prognostic marker to the clinician is its ability to predict specific patterns of tumor recurrence in order to permit the most appropriate treatment in any given patient. Thus, we cannot tell whether the lack of expression of bcl-2 protein is predictive of an increased probability of a local, regional, or distant recurrence. The authors suggest that lung cancers that are inoperable according to current criteria can be reconsidered for surgical treatment if they are positive for bcl-2, but this is erroneous, since they present no evidence that the survival benefit conferred by the expression of bcl-2 outweighs the serious adverse prognostic implications of surgical or medical inoperability. The current criteria for inoperability in patients with non-small-cell lung cancer include the presence of tumors that are too extensive to permit a curative resection or factors such as poor pulmonary function that would not permit the patient to tolerate a major lung resection. No prognostic marker can override the use of sound clinical judgment in dealing with these limitations.

Harry R. Katz, M.D.
Jefferson Radiation Oncology Center, Pittsburgh, PA 15236

3 References

1. 1

   Pezzella F, Turley H, Kuzu I, et al. bcl-2 protein in non-small-cell lung carcinoma. N Engl J Med 1993;329:690-694
   Full Text | Web of Science | Medline

2. 2

   DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 4th ed. Philadelphia: J.B. Lippincott, 1993.
   

3. 3

   Gail MH, Muenz L, McIntire KR, et al. Multiple markers for lung cancer diagnosis: validation of models for localized lung cancer. J Natl Cancer Inst 1988;80:97-101
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Dr. Katz raises a number of interesting points, but we believe that some of his anxieties are misplaced.

He is worried about the practical use of bcl-2 as a tumor marker because it was expressed in a minority of the patients. We understand such a concern and indeed clearly stated in our paper that there are not yet sufficient data to establish the use of the expression of bcl-2 as a tumor marker in lung diseases.

The second point he raises, on the inverse relation between T and N stages and the expression of bcl-2, is incorrect. We stated that “there was no association of bcl-2 expression with the grade of tumor differentiation . . . , the T stage . . . , or the N stage.” Furthermore, we did not suggest that “lung cancers that are inoperable according to current criteria can be reconsidered for surgical treatment.” We did raise this possibility, commenting that it would need to be answered by a formal investigation. Clearly, patients with poor respiratory reserve are not going to be affected by this type of assessment. However, those with extensive nodal involvement (more than stage N1), who would not normally be considered for surgery, could be assessed further, because the value of the expression of bcl-2 as a prognostic factor is independent of the nodal status. Furthermore, it will be particularly important to examine the relation between the expression of bcl-2 and sensitivity to drug and radiation therapy, especially if patients with low levels of protein are more sensitive to these methods and would otherwise have a poor prognosis.

Optimization of the results currently achievable with radiation and chemotherapy, with or without surgery, may be of value. We do not share Dr. Katz's fear that the use of markers such as the expression of bcl-2 will override sound clinical judgment but rather hope that they will perhaps become part of it.

Francesco Pezzella, M.D.
Adrian Harris, D.Phil.
Kevin C. Gatter, D.Phil.
John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom

Citing Articles (2)

Citing Articles

1. 1

   Jiannong Li, Jean Viallet, Eric B. Haura. (2008) A small molecule pan-Bcl-2 family inhibitor, GX15-070, induces apoptosis and enhances cisplatin-induced apoptosis in non-small cell lung cancer cells. Cancer Chemotherapy and Pharmacology 61:3, 525-534
   CrossRef

2. 2

   M.V Fleming, D.G Guinee, W.S Chu, A.N Freedman, N.E Caporaso, W.P Bennett, T.V Colby, H Tazelaar, S.L Abbondanzo, J Jett, P Pairolero, V Trastek, L.A Liotta, C.C Harris, W.D Travis. (1998) Bcl-2 immunohistochemistry in a surgical series of non-small cell lung cancer patients. Human Pathology 29:1, 60-64
   CrossRef