Search

Objective: To investigate gene mutations of epidermal growth factor receptor (EGFR) and K-ras in Chinese patients with non-small cell lung cancer (NSCLC) and its clinicopathological significance, and to analyze the correlation between these mutations and tumor response to erlotinib treatment., Methods: Mutations of exons 18, 19, 20 and 21 of the EGFR and codons 12, 13 of the K-ras in 301 cases of NSCLC were detected by PCR-amplification and gene sequencing. The relationship between the mutations and clinicopathological characteristics of the 301 patients was analyzed., Results: EGFR mutations were present in 32.9% (99/301) of the samples: 3 mutation in exon 18, 59 in exon 19, 2 in exon 20, and 35 in exon 21. Mutations of K-ras were present in 4.7% (14/301) of the samples: 13 in codon 12 and 1 in codon 13. EGFR mutations were never found in tumors with K-ras mutations, suggesting a mutually exclusive relationship. EGFR mutations were more common in adenocarcinomas, non-smokers and females. Seven out of 10 erlotinib-treated patients with disease control carried EGFR mutation., Conclusion: The frequency of EGFR mutation in Chinese NSCLC patients is higher than that in Westerners, but the frequency of K-ras mutation is quite opposite. Combined detection of EGFR gene and K-ras gene mutation may help clinicians to choose patients who may gain benefit from EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment, and to predict their response to erlotinib treatment and prognosis.

Objective: To investigate the mRNA and proten expression of coxsackievirus and adenovirus receptor (CAR) in the corresponding normal lung tissue, para-neoplastic tissue and lung cancer tissue, and the correlation of CAR expression with the carcinogenesis as well as the expression difference in various clinicopathologic parameters., Methods: The expression of CAR mRNA and protein in the samples from 32 lung cancer patients was determined by RT-PCR and Western blot, respectively., Results: The expression level of CAR mRNA and protein in normal lung tissue, paraneoplastic tissue and cancer tissue were 1.000 +/- 0.012, 1.048 +/- 0.035, 1.282 +/- 0.072, and 0.902 +/- 0.038, 0.944 +/- 0.042, 1.08 +/- 0.052, respectively, with a statistical significance among the groups (P = 0.022, P = 0.007, P = 0.009, P = 0.027). There was a statistically significant positive correlation between expression of CAR mRNA and that of CAR protein (r = 0.448, P = 0.026). The expression levels of CAR were significantly different among different pathological types (P = 0.012), with a high level of CAR in all 7 bronchiolo-alveolar carcinoma (BAC, P = 0.029). However, there was no statistical significance in other clinicopathologic parameters (P > 0.05), including gender, age, smoking or not, tumor size, with or without lymph node metastasis and TNM stage., Conclusion: The expression of CAR mRNA and protein in cancer tissue samples are significantly higher than that in the normal and paraneoplastic samples, indicating that CAR might play a crucial role in the carcinogenesis. It may become a new potential prognostic marker for lung cancer patients.

Objective: To study the expression and clinical significance of cytokeratin subtypes CK7 and CK20 and thyroid transcription factor-1 (TTF-1) in bronchioloalveolar carcinoma (BAC), and to investigate the value of these factors in identification of the prognosis of BAC., Methods: Eighty-one specimens of BAC resected during operation, 68 of non-mucinous type and 13 of mucinous type, underwent immunohistochemical examination to detect the expression of CK7, CK20, and TTF-1. The value of these 3 factors in the identification of the prognosis of BAC was examined by survival analysis., Results: All specimens showed positive expression of CK7, CK20, and TTF-1. There was no significant differences in CK7 expression rate among different ages, clinical stages, and pathological subtypes (all P > 0.05). Compared with that in the BAC of stage III and that of BAC of non-mucinous type, the CK20 positive rates of the BAC of stage I - II and mucinous type were both significantly higher (chi(2) = 3.928, P < 0.05, and chi(2) = 11.512, P < 0.05). The TTF-1 positive rates of the BAC of stage III and nonmucinous type were significantly higher than those of stage I - II and mucinous type respectively (chi(2) = 7.840, P < 0.05, and chi(2) = 19.497, P < 0.05). There was a statistically significant positive correlation between the expression of CK7 and expression of TTF-1 (r = 0.257, P = 0.021). Univariate analysis showed that the main prognostic factors were TTF-1 expression (P = 0.017), clinical stage (P = 0.000), tumor diameter (P = 0.017) and N stage (P = 0.000). Strata analysis suggested that in the nonmucinous type BAC patients the survival time of those positive for TTF-1 expression was superior to those negative for TTF-1 (P = 0.009); and in the stage III BAC patients the survival time of those positive for TTF-1 was superior to those negative for TTF-1 (P = 0.022). Cox regression analysis suggested that TTF-1 (P = 0.035), TNM stage (P = 0.000), tumor diameter (P = 0.034), and N stage (P = 0.000) were independent factors affecting the prognosis., Conclusion: There is a statistically significant positive correlation between the expression of CK7 and the expression of TTF-1. TTF-1 and CK20 provide a new evidence for the molecular staging of BAC. TTF-1, TNM stage, tumor diameter and N stage are all independent factors affecting the prognosis of BAC.