Proliferation, growth, and differentiation of cells are strictly controlled by the signal system of epidermal growth factor receptor (EGFR). If any link of the EGFR signals system is interfered with or damaged, the proliferation, growth, and differentiation of cells would become uncontrolled. EGFR is overexpressed in a variety of malignant tumors, such as non-small-cell lung cancer, colorectal cancer and breast cancer. Results of the study have proved that EGFR overexpression is closely associated with mutations and variants of the EGFR genes, whose mutations and variants are associated with occurrence, metastasis, and prognosis of different types of tumors, including lung cancer. This study is aimed at investigating whether the polymorphisms of CA simple sequence repeat in intron 1 (CA-SSR1), -216G/T, and R497K in the EGFR are able to induce EGFR activation and whether overexpression is associated with pleural metastasis of lung adenocarcinoma. A total of 432 lung adenocarcinoma patients with pleural metastasis (metastasis group) and 424 patients with lung adenocarcinoma but without pleural metastasis (nonmetastasis group) were enrolled in this study. For all patients, the CA-SSR1 genotypes were determined by capillary electrophoresis, polymerase chain reaction amplification, and direct DNA sequencing, and the R497K and -216G/T genotypes were determined by polymerase chain reaction amplification and direct DNA sequencing. EGFR expression was evaluated by immunohistochemical staining in primary tumor tissues with different -216G/T, R497K, and CA-SSR1 genotypes. Our results showed significant differences between pleural metastasis and nonmetastasis groups in the genotype and allele distribution of -216G/T, R497K, and CA-SSR1 polymorphisms of the EGFR gene. The -216T allele, Arg allele, and shorter CA-SSR1 (<17) had significantly increased risks of pleural metastasis compared with the -216G allele, Lys allele, and longer CA-SSR1 (≥17), respectively. The expression of EGFR was higher in patients with genotypes of -216T/T or -216G/T, Arg/Arg or Arg/Lys, and shorter CA-SSR1 (<17) than that in patients with genotypes of -216G/G, Lys/Lys, and longer CA-SSR1 (≥17), respectively. These results indicate that -216G/T, R497K, and CA-SSR1 polymorphisms are associated with the risk of pleural metastasis of lung adenocarcinoma, which may be related to the overexpression of EGFR protein induced by -216G/T, R497K, and CA-SSR1 polymorphisms.

Numerous mutations and variants in the epidermal growth factor receptor (EGFR) gene have been demonstrated to be associated with the occurrence, metastasis and prognosis of various types of tumors, including lung cancer. Thus, the present study aimed to investigate whether -216G/T (rs712829), a functional polymorphism of the EGFR promoter that is able to induce EGFR activation and overexpression, is associated with the pleural metastasis of lung adenocarcinoma. The study subjects were comprised of 326 patients with primary lung adenocarcinoma and 312 matched cases with pleural metastasis. The -216G/T genotypes were determined in all subjects by PCR amplification and direct DNA sequencing, and EGFR expression was also evaluated by immunohistochemical staining in the primary tumor tissues with various -216G/T genotype backgrounds. The results showed that the frequencies of allele T and genotypes G/T and T/T in the pleural metastasis group were significantly higher compared with those in the non-metastasis group, with adjusted ORs of 1.46 (95% CI, 1.015–1.963) for G/T and 1.97 (95% CI, 1.051–3.152) for T/T. Furthermore, the expression of the EGFR protein was higher in the primary lung adenocarcinoma tissues with -216T/T and -216G/T compared with those with -216G/G (P<0.05). These results collectively indicate that the -216G/T polymorphism in the EGFR promoter is associated with the risk of the pleural metastasis of lung adenocarcinoma and that this effect may be associated with -216G/T-induced overexpression of the EGFR protein.

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482 Background: The standard of care for locally advanced SCCA of the AC is 5-fluorouracil (5-FU)/mitomycin C (MMC) with concurrent XRT. C was evaluated with 5-FU in 2 large phase III studies (RTOG 98-11 and ACT II) to establish superiority over 5-FU/MMC. Neither study showed significant differences for disease-free survival (DFS) or overall survival (OS). RTOG 98-11 reported reduced colostomy-free survival (CFS) in the C-induction arm; no differences were noted in the ACT II study. We present our 20-year experience with C for locally advanced SCCA of the AC which has been adopted as the standard unless contraindicated. Methods: A retrospective, single institution analysis for locally advanced SCCA of the AC was completed in patients (pts) that received concurrent 5-FU/C/XRT from 1989-2009. Medical records were reviewed for history of STDs, chronic immunosuppression, stage, dose of XRT, toxicity, clinical response (CR), recurrence, and OS. Multidisciplinary management included surgical, radiation, and medical oncologists. OS, DFS, and CFS were calculated using the K-M method. The log-rank test was used to compare OS among these subgroups. Results: 185 pts were identified (51 M:134 F). The median age was 56 (35-83 y.o.). AJCC stage was I (n = 25); II (n = 76); IIIA (n = 36); and IIIB (n = 48). The median XRT dose was 55 Gy in 30 fractions. 181 pts were evaluable for response; 4 were lost to follow up. Complete CR (cCR) was noted in 169 pts (93%); partial response (n = 12); 6 pts received an APR. After a median follow up of 8.6 years, 14 pts (8%) developed local recurrence; 11 received salvage surgery. 16 pts (9%) developed distant metastases (DM). The 5-yr DFS = 81%, 5-yr OS = 85% and 5-yr CFS was 88%. By univariate analysis, N-stage was a poor prognostic indicator for 5-yr DFS (p = 0.02) and DM (p = 0.046) but not OS or CFS. Increased T-stage correlated with salvage surgery (p = 0.005). Conclusions: Cisplatin-based chemoradiation for locally advanced SCCA of the anal canal resulted in favorable DFS, OS, and CFS compared to historical data and phase III studies. Platinum-based therapy for anal cancer appears to be an acceptable alternative to MMC and should be considered as a standard option for locally advanced disease. No significant financial relationships to disclose.