Expression of syndecan‐1 and expression of epidermal growth factor receptor are associated with survival in patients with nonsmall cell lung carcinoma

Abstract

BACKGROUND Recently, the authors identified molecular signatures and pathways associated with nonsmall cell lung carcinoma histology and lung development. They hypothesized that genetic classifiers of histology would provide insight into lung tumorigenesis and would be associated with clinical outcome when evaluated in a broader set of specimens. METHODS Associations between patient survival and immunostaining for 11 representative histologic classifiers (epidermal growth factor receptor [EGFR], CDK4, syndecan‐1, singed‐like, TTF‐1, keratin 5, HDAC2, docking protein 1, integrin α3, P63, and cyclin D1) were examined using a tissue microarray constructed from nonsmall cell lung carcinoma specimens. RESULTS Sixty‐three tumors were examined, including 43 adenocarcinomas, 11 large cell carcinomas, and 9 squamous cell carcinomas. Sixty‐three percent of tumors were clinical Stage I lesions, and 37% were Stage II–III lesions. In a multivariate analysis that controlled for age, gender, and race, syndecan‐1 expression was found to be associated with a significant reduction in the risk of death (hazard ratio, 0.31 [95% confidence interval, 0.18–0.87]; P < 0.05). Multivariate analysis also indicated that EGFR expression was associated with a significant reduced risk of death. CONCLUSIONS The authors demonstrated that expression of either of the nonsmall cell lung carcinoma subtype classifiers syndecan‐1 and EGFR was associated with a 30% reduction in the risk of death, with this reduction being independent of histology and other confounders. The results of the current study suggest that loss of expression of these histologic classifiers is associated with biologic aggressiveness in lung tumors and with poor outcome for patients with such tumors. If their significance can be validated prospectively, these biomarkers may be used to guide therapeutic planning for patients with nonsmall cell lung carcinoma. Cancer 2004. © 2004 American Cancer Society.

Expression of p63, ttf–1 and maspin in non-small cell lung carcinoma and their effect on the prognosis and differential diagnosis

“…However, they did not find p63 to be associated with survival in NSCLC cases. No p63 staining was found in ACs in some studies while others reported positivity rates of 10% to 65% (3,4,10,19,21,(24)(25)(26)(27)(30)(31)(32). However, studies reporting negative results with p63 in ACs had quite low numbers of patients compared to those with positive results where the number was 70 to 90.…”

Clinical significance of syndecan-1 and versican expression in human epithelial ovarian cancer

“…It also binds to members of the heparin-binding growth factor family such as the basic fibroblast growth factor (bFGF), which is the best-studied example; hepatocyte growth factor (HGF); a splice variant of platelet-derived growth factor (PDGF); heparin-binding epidermal growth factor (EGF); vascular endothelial growth factor (VEGF); neuregulins; and others (4). The loss of epithelial syndecan-1 expression has been associated with poor prognosis in some forms of cancer (10)(11)(12)(13)(14)(15)(16)(17). Recently, stromal syndecan-1 expression was found to be correlated with a devastating clinical course in several kinds of cancers (11,(17)(18)(19).…”

Epidermal growth factor receptor protein expression in lung cancer and survival analysis

“…21 Similarly studies done by Ucvet et al, Shah et al and Rusch et al found improved survival among EGFR positive patients. 16,22,23 26 Thatcher et al and Hirsch et al also found better survival in patients receiving Geftinib who have EGFR positivity. 27,28 Treatment with radiotherapy sequentially or concurrently with chemotherapy may provide benefit to the patients with unresectable locally advanced stage III NSCLC.…”

“…14 We found EGFR expression more common in adenocarcinoma subtype (58.8%) followed by squamous cell carcinoma (23.5%) which is in agreement with Korean study done by Ahn et al and study done in US by Shah et al but different from the Japanese population, Suzuki et al and in the Italian population, Ludovini et al, who found EGFR overexpression common in squamous cell carcinoma. 12,15,16,17 EGFR overexpression and its relation to survival in patients with NSCLC has been studied for many years, but with conflicting results. We did not find any statistically significant association between EGFR status with survival (HR-1.13, p-0.75) similar to observations by Deeb et al and Lee et al who did not find association between EGFR expression and survival.…”