Characteristics of long-term survivors of untreated lung cancer
Introduction
Lung cancer consists of a heterogeneous group of tumors with distinct biological and clinical characteristics. There are four major subtypes of lung cancer: squamous cell carcinoma, adenocarcinoma, large cell carcinoma (referred to as non-small cell lung cancer—NSCLC) and small cell lung cancer. The only hope for the significant survival of those patients with NSCLC is tumor resection. However, in more than 70% of all patients suffering from lung cancer, the tumor is inoperable at the time of diagnosis. Furthermore, even with treatment, more than 85–90% of the patients die shortly following their diagnosis.
However, it has become apparent that a number of patients with locally advanced tumors have continued to live for prolonged periods, and in some cases, appear to be cured by operation alone.
Although the prognostic variables determining short-term survival have been well described [1], [2], [3], [4], [5], [6], [7], relatively little attention has been paid to factors associated with long-term survival. In an attempt to identify these factors, we investigated the expression of several markers in tumors of patients with a long and a short survival after resection of locally advanced stage III NSCLC. The evaluated biomarkers were chosen according to our own experience, and they are among the most often reported ones in the literature as of prognostic importance: oncogenes (fos, ras, jun, erbB-1, erbB-2), tumor suppressor genes (p53, Rb), markers of angiogenesis (VEGF, VEGFR-1, bFGF, FGFR-1, TSP), resistance-related factors (P-170, GST, MT, TS, MGMT, Cat, HSP-70), markers of cell proliferation (cyclin A, PCNA-index, S-phase fraction) and markers of apoptosis (fas/CD95, bcl-2, apoptotic index (AI)).
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Patients and tumors
From patients undergoing resection for NSCLC at the Chest Hospital Heidelberg-Rohrbach, Germany, 21 with squamous cell lung carcinomas and postoperative stage III tumors and a survival of 260 weeks (5 years) or longer were identified and selected for this study. For comparison, another group of 53 patients with matched patient and tumor characteristics, who died of tumor recurrence within 100 weeks (2 years), was selected from the same population. As the majority of recurrent disease can
Results
The characteristics of the study population are shown in Table 1. The long and short survival group were similar in most aspects, except for survival. The average survival of the long survival group was 292 weeks, whereas the survival in the short survival group was 36 weeks (Fig. 1). All patients had squamous cell carcinoma of the lung and stage III tumors. The differentiation grade of the tumors was similar in both groups.
The results of the immunohistochemical evaluation of the tumor samples
Discussion
In an attempt to identify prognostic factors in NSCLC associated with long-term survival, we evaluated several immunohistochemical markers in long-term (⩾5 years) and short-term survivors (⩽2 years) of resected NSCLC. We found significant differences in the two survival groups with some oncogenes (c-fos, N-ras, p53), with the pro-apoptotic marker CD95 and with markers of proliferation (S, G2, SG2M, cyclin A). No differences were found with the expression of marker of angiogenesis and of
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