Incidence of ras oncogene activation in lung carcinomas in Hong Kong.

BACKGROUND. In Hong Kong, lung carcinomas contribute to the majority of cancer deaths among Chinese. Point mutational activation of ras oncogenes has been observed in several populations. The incidence of these mutations in Hong Kong lung carcinomas was investigated. METHODS. Lung resections obtained from 52 Chinese patients whose conditions were newly diagnosed as non-small cell lung cancer, paraffin sections from 29 Chinese patients with previously diagnosed adenocarcinoma of the lung, and paraffin sections from 49 squamous cell carcinomas were examined for the presence of point mutations in Ki-ras codon 12, N-ras codon 61, and Ha-ras codon 12 oncogenes by allele-specific hybridization after specific amplification of appropriate regions of the DNA using the polymerase chain reaction. RESULTS. Among the 130 lung carcinomas investigated, Ki-ras point mutations were detected in seven cases, of which six were adenocarcinomas and one a squamous cell carcinoma. No mutations were detected in the N-ras and Ha-ras codons. CONCLUSIONS. The incidence of Ki-ras codon 12 point mutational activation in Chinese patients with adenocarcinomas was 6 of 63 (9.5%). The incidence of Ki-ras 12 point mutational activation among men with lung adenocarcinomas in Hong Kong (6 of 32 patients, 18.8%) is significantly different from that in women in Hong Kong (0 of 31 patients, 0%). Although ras oncogenes are implicated as having a role in the development of lung adenocarcinomas, especially among smokers, it is clear from these data that they are not associated with the unusually high incidence of lung adenocarcinomas among women in Hong Kong.     

Mutational Damages in Malignant Lung Tumors

Background: Today, genomic changes are an important cause of the occurrence, growth and progression of cancer. Technological advances in cancer genomic analysis platforms have made it possible to identify genomic alterations that may influence response to lung cancer treatment. Methods: The study examined tumor growth-inhibiting oncogenes and genes responsible for cell growth and division to identify mutations characteristic of malignant lung tumors. The mutations were studied in 400 postoperative samples after amplifying p53 and HRAS fragments and p53, p21Waf1, MDM2 mRNA. p53 or p21Waf1 were expressed in 50% of squamous cell carcinomas and adenocarcinomas of the lung. Results: The study examined tumor growth-inhibiting oncogenes and genes responsible for cell growth and division to identify mutations characteristic of malignant lung tumors. The mutations were studied in 400 postoperative samples after amplifying p53 and HRAS fragments and p53, p21Waf1, MDM2 mRNA. p53 or p21Waf1 were expressed in 50% of squamous cell carcinomas and adenocarcinomas of the lung. HRAS mutations were present in most squamous cell carcinomas and adenocarcinomas of the lung. EcoR1- and Pst1- restriction enzymes destroyed the RT-PCR product of the p53 and p21Waf1 mRNA and increased the level of detected mutations in lung adenocarcinoma to 75% and 50 %, respectively. EGFR mutations were more frequent in lung adenocarcinoma than in lung squamous cell carcinoma. Mutations in EGFR exons 19 and 21 found in 65 of 263 lung tumor samples indicated the tumor sensitivity to EGFR tyrosine kinase inhibitors. EGFR deletions in exon 19 occurred mainly in adenocarcinoma, L858R mutations in EGFR exon 21 were quite common in lung adenocarcinoma. Conclusion: The mutations detected in most squamous cell carcinomas and adenocarcinomas of the lung could be used to diagnose and predict the disease severity and targeted therapy efficacy.     

Immunohistochemical study of oncogene-related products in human gastrointestinal malignancies--expression of ras p 21, fes p 85 and EGF receptor

An immunohistochemical examination by the avidin-biotin-peroxidase complex method was carried out to assess the expression of oncogene-related products, i.e., ras p 21 protein, fes p 85 protein and epidermal-growth-factor (EGF) receptors, in human gastrointestinal malignancies. The presence of ras p 21, fes p 85 and EGF receptors was detected in 48%, 62%, and 62% of 29 colorectal carcinomas and in 65%, 65% and 40% of 20 gastric cancers, respectively. More than one oncogene protein was demonstrated in 18 of 29 colorectal carcinomas and in 10 of 20 gastric cancers. These results suggest that multiple oncogenes are important in the occurrence and progress of gastrointestinal malignancies.     

Clinicopathologic characteristics of adenosquamous carcinoma of the lung

Fifty-six cases of surgically resected adenosquamous carcinoma of the lung were studied clinicopathologically, and their outcome was compared with that of adenocarcinomas and squamous cell carcinomas of the lung. The frequency rate of adenosquamous carcinoma was 2.6% of 2160 primary lung cancers resected in the National Cancer Center Hospital (Tokyo, Japan). The survival curves of patients with adenosquamous carcinomas, adenocarcinomas, and squamous cell carcinomas indicated that the outcome of adenosquamous carcinoma was poorer than that of adenocarcinomas and squamous cell carcinomas, particularly in Stages I and II. The amount of adenocarcinoma component did not affect the survival rate, although the histologic features of metastatic lymph nodes was somewhat influenced by the histologic type of the primary tumors. The histologic subtype of adenosquamous carcinoma was one of the independent prognostic determinants.     

Immunocytochemical study of RAS oncoprotein in cytologic specimens of primary lung tumours

We have examined the distribution of ras p21 oncoprotein expression in cytologic specimens from 73 primary bronchial carcinomas using an immunocytochemical analysis. The cytologic preparations studied represent the two major groups of histological types of lung cancer: Small Cell Lung Carcinoma (SCLC) and Non-Small Cell Lung Carcinoma (NSCLC) (squamous cell carcinoma and adenocarcinoma). The differential expression of ras p21 oncoprotein correlated with histological classification and was found in 30% of 23 small cell lesions, 61% of 28 squamous cell lung carcinomas and 32% of 22 adenocarcinomas. The ras p21 oncoprotein was commonly expressed in NSCLC cases (48%) as compared to SCLC cases (30%).     

THE STUDY ON RELATIONSHIP BETWEEN CIGARETTE SMOKING AND THE p53 PROTEIN AND P21 PROTEIN EXPRESSION IN NON-SMALL LUNG CANCER

This paper discusses the relationship betweencigarette smoking and the p53 protein and P21 proteinexpression by the immunohistochemical analysis in 93cases with lung cancer in which squamous cell carcinomaaccounted for 45 cases, adenocarcinoma 48 cases. Theresults showed that positive proportion of p53 proteinexpression was 74.20% (28 of 37 squamous cell carcinoma,21 of 30 adenocarcinomas) in cigarette smoking groupwith lung cancers, and 38.46% (3 of 8 squamous cellcarcinoma, 7 of 18 adenocarcinomas) in nonsmokinggroup with lung cancers. The difference was statisticallysignificant. Odds ratio was 4.14 and confidence limitsfor OR was 1.42-12.52. A dose-related presents in thep53 protein expression for the smoking amount andsmoking years. The positive proportion of P21 proteinexpression was 79.31% (21 of 28 squamous cell carcinoma,25 of 30 adenocarcinomas) in cigarette smoking groupwith lung cancers, and 82.75%(10 of 11 squamous,14 of18 adenocarcinomas) in nonsmoking group with lungcancers, the difference     

A study on p16, pRb, cdk4 and cyclinD1 expression in non-small cell lung cancers

To observe the expression of p16, pRb, cdk4 and cyclinD1 in non-small cell lung cancers, 104 cases of resected lung cancers were collected, which included squamous cell carcinomas, adenocarcinomas and large cell carcinomas. Immunohistochemistry assay was carried out. The results showed that 67% of squamous cell carcinomas and 46% of adenocarcinomas expressed p16, 64% of squamous cell carcinomas and 85% of adenocarcinomas expressed pRb and 66% of cancers expressed p16 or pRb. About 70% of the tumors expressed cyclinD1. More than 90% of the tumors expressed cdk4 and there was an increased trend with decreasing differentiation of both squamous cell carcinomas and adenocarcinomas. Sixty-seven percent of the highly differentiated and 100% of the poorly differentiated squamous cell carcinomas expressed cdk4. The aberrant p16 and pRb gene product expression played a significant role in the development and histological subtype of lung cancers by conditioning the biological behavior of NSCLC. cdk4 was an important factor in histological differentiation.     

Quantitation of Harvey ras p21 enhanced expression in human breast and colon carcinomas

Molecular studies have demonstrated increased expression of the Harvey (Ha) ras oncogene in human breast and colon carcinomas. With the use of a direct-binding liquid competition radioimmunoassay (RIA), capable of providing truly quantitative analysis of the 21,000-dalton (p21) ras oncogene and protooncogene products, absolute levels of Ha-ras p21 have been determined in human breast and colon carcinomas, benign lesions, and/or their respective normal tissues. Enhanced Ha-ras expression was documented in 66% of breast and 100% of colon carcinomas as compared with their normal counterparts, with levels in breast carcinomas ranging from 10.1 to 50.4 pg ras p21/micrograms protein and those in colon carcinomas ranging from 18.4 to 51.7 pg ras p21/micrograms protein. Some dysplastic lesions of the breast and colon also contained elevated Ha-ras p21. Relative levels of Ha-ras p21 expression, detected by competition RIA, correlated with percent Ha-ras p21-positive cells as determined by immunohistochemical assays. By use of liquid competition RIA and immunohistochemical assays, it has been shown that levels of ras p21 expression did not always correlate between primary and metastatic colon lesions of the same patient. The use of the quantitative RIA and semiquantitative immunohistochemical assays, in concert with cDNA probes for identification of specific ras point-mutated oncogenes or protooncogenes, may now provide the means for definitive quantitative analyses of ras p21 in human carcinomas and benign lesions.     

Rare Occurrence of ras and p53 Gene Mutations in Mouse Stomach Tumors Induced by N–Methyl–N–nitrosourea

The incidence of point mutations of H–, K– and N– ras and p53 oncogenes in male BALB/c mouse stomach tumors induced with A^r–methyl–A^r–nitrosourea (MNU) was examined by direct sequencing and PCR single–strand conformation polymorphism (PCR–SSCP). A mutation of GGT to AGT at K–ras codon 12 was found by SSCP in one adenocarcinoma from a total of 19 specimens including 5 adenocarcinomas, 9 adenomatous hypcrplastic regions, 1 squamous cell carcinoma and 4 normal–like stomach regions from 4 mice. No mutations were detected by direct sequencing of H–, K– and N–ras oncogenes at exons 1 (codons 12 and 13) and 2 (codon 61) in a total of 26 specimens comprising 10 adenocarcinomas, 10 adenomatons hyperplastic regions, 2 squamous cell carcinomas and 4 normal–like stomach regions from 6 mice. No mutations were detected by direct sequencing ofp53 oncogene at exons 5, 6, 7 and 8 in a total of 30 specimens including 13 adenocarcinomas, 8 adenomatous hyperplastic regions, 2 squamous cell carcinomas, 1 papilloma and 6 normal–like stomach regions from 7 mice. These results suggest that ras and p53 oncogenes do not play a role in mouse stomach carcinogenesis induced by MNU.     

Prognostic significance of the expression of ras oncogene product in non-small cell lung cancer.

The clinical significance of ras oncogene expression in non-small cell lung cancer was evaluated in 116 surgically treated patients. Archival paraffin sections of the tumors were analyzed immunohistochemically using anti-ras p21 monoclonal antibody (MoAb) rp-35, and p21 staining was correlated with clinicopathologic parameters and survival. Positive reactions (+ and ++) were observed in 72.5% of the adenocarcinomas and 55.6% of the squamous cell carcinomas studied. The T1 tumors showed a ++ reaction less frequently than T2 and T3 tumors (P less than 0.05). Stage I tumors also were less reactive with MoAb rp-35 than tumors in more advanced stages (P less than 0.05). Survival analysis showed that patients with p21-negative tumors had significantly longer survival times (a 5-year survival rate of 64.1%) than those with p21 + tumors (38.0%, P less than 0.05) or those with p21 ++ tumors (11.5%, P less than 0.005). The significant correlation between p21 staining and patient survival was independent of histologic type, stage of disease, tumor or node status, and the resectability of tumors. On Cox's multivariate analysis, p21 staining was a major and independent prognostic determinant of survival. These results suggest that enhanced ras p21 expression may be one of the important biologic and clinical markers indicating the malignant potential of non-small cell lung cancer.     

Expression pattern of the scaffold protein IQGAP1 in lung cancer

IQGAP1 is a scaffold protein whose function relates to signal transduction, cell adhesion, local invasion, and distant metastasis of cancer cells. We examined the expression patterns of this protein and clinicopathologic features of lung cancer, and the antibody against IQGAP1 was used for immunohistochemical analysis. Of the 70 surgical specimens examined, there were 40 adenocarcinomas, 19 squamous cell carcinomas, 5 large cell carcinomas, 3 small cell carcinomas, 2 carcinoid tumors, and 1 mucoepidermoid carcinoma. The localization of IQGAP1 was classified into three types: 1) cytoplasmic, 2) membranous, and 3) reduced expression. In adenocarcinoma, the 3 types were observed equally, and differentiation grade was related to the expression pattern. The cytoplasmic type was common in well-differentiated adenocarcinomas, and membranous or reduced expression was frequently seen in moderately- or poorly-differentiated adenocarcinomas. In squamous cell carcinoma, the membranous type was most common. Although the staining pattern of IQGAP1 did not correlate with the positivity of regional lymph nodes, survival in those patients with a cytoplasmic type was significantly better than others with adenocarcinoma (p=0.0144). Expression typing of IQGAP1 in lung cancer was associated with histologic type and can be used to predict survival in patients with adenocarcinoma of the lung.     

p73和p63蛋白在胰腺癌组织中过表达的意义

目的:探讨p53家族新成员p73和p63蛋白在胰腺癌组织中过表达的意义。方法:应用免疫组化LSAB法检测75例人胰腺癌组织中p73和p63蛋白的过表达。结果:p73和p63蛋白在人胰腺癌中的过表达率分别为46·7%(35/75)和42·7%(32/75),p73蛋白在胰腺囊腺癌中的过表达率88·9%(8/9)明显高于导管腺癌41·8%(23/55),P=0·009,且p73蛋白过表达与胰腺癌淋巴结转移、肿瘤大小、神经侵犯和p53表达呈显著负相关性,P<0·05;在腺鳞癌或腺癌伴鳞状上皮化生中p63蛋白的过表达率(100%,13/13)明显高于导管腺癌(40·0%,22/55),P=0·007,但p63蛋白过表达与胰腺癌临床病理学指标及p53和增殖细胞核抗原(pro-liferatingcellnuclearantigen,PCNA)表达间无明显相关性。结论:p73蛋白低表达可能在胰腺癌发生中起重要作用;p63蛋白过表达与腺鳞癌或腺癌鳞化有关。     

RON及其变异体在肺癌中的表达

目的研究RON及其变异体在肺腺癌中的表达及意义。方法应用免疫组化方法检测106例肺腺癌及35例肺鳞癌中RON的表达情况,并结合临床资料进行统计学分析;通过Western-Blot技术检测31例新鲜肺腺癌组织及9例肺鳞癌组织中RON及其变异体的表达情况,并对RON在不同组织学分级和不同组织学类型中的表达进行统计学分析。结果RON在肺腺癌及鳞癌中都有不同程度的表达,两组比较RON的表达差异具有统计学意义（P〈0.05）;不同分化程度的肺腺癌比较,RON的表达也有差异,低分化的肺腺癌明显高于中分化的腺癌和高分化的腺癌（P〈0.05）;Western-Blot结果显示在肺腺癌和肺鳞癌中均有RON表达;在肺腺癌中观察到RON的变异体,而肺鳞癌中则没有。结论肺癌组织中有RON的过表达,并且肺腺癌中RON的表达明显高于鳞癌（P〈0.05）。肺腺癌中RON的表达与肿瘤分级相关,并存在变异体,而鳞癌则无变异体的表达。     

Prognostic Value of Prepro-Gastrin Releasing Peptide in Lung Cancer Patients; NCI-Prospective Study

Background: Prior series investigated the expression of prepro-gastrin releasing peptide (prepro-GRP) in the peripheral blood of lung cancer patients. Our aim was to assess any prepro-GRP role as a prognostic factor for small cell lung cancer (SCLC) and NSCLC and correlations with clinical presentation and treatment outcome. Methods: A prospective study was conducted during the time period from the beginning of January 2012 till the end of January 2014. Prepro-GRP expression was analysed using a nested RT-PCR assay in peripheral blood of 62 untreated lung cancer patients attending the National Cancer Institute (NCI), Cairo University, and 30 age and sex matched healthy volunteers. Results: Among the 62 lung cancer cases, there were 24 (38.7%) SCLC, and 38 (61.3%) NSCLC (10 squamous cell carcinomas, 12 adenocarcinomas, 11 large cell carcinomas, 4 undifferentiated carcinomas, and 1 adenosquamous carcinoma). Twenty six patients (41.9%) were prepro-GRP positive. Prepro-GRP expression was higher (58.3%) among SCLC patients compared to NSCLC (squamous cell carcinoma (15.4%), large cell carcinoma (36.4%), and adenocarcinoma (25%)). Mean OS among prepro-GRP negative cases was longer than that among preprogastrin positive cases (17.6 vs 14.9 months). The mean PFS durations among preprogastrin negative versus positive cases were 7.7 vs 4.6 months (p= 0.041). No difference in response to chemotherapy was identified between the groups (p=0.983). Conclusion: Prepro-GRP is suggested to be a useful prognostic marker for lung cancer patients, especially with the fast- growing, bad prognostic SCLC type. More studies should aim at detailed understanding of the mechanisms of prepro-GRP action and its use in monitoring the response to treatment in a larger cohort.     

The expression of Bcl-2 family proteins differs between nonsmall cell lung carcinoma subtypes

BACKGROUND: Proteins of the Bcl-2 family play a key role in the control of apoptosis and carry out both proapoptotic and antiapoptotic functions. However, with the exception of Bcl-2 itself, little is known about the expression of these potentially critical proteins in nonsmall cell lung carcinoma. METHODS: Immunohistochemistry was used to study the expression of Bcl-2 and 6 other Bcl-2 family proteins in a pilot series of 41 archival nonsmall cell lung carcinoma specimens (19 adenocarcinomas and 22 squamous cell carcinomas). RESULTS: Overexpression of the apoptosis inhibitors Bcl-2 and Bcl-X(L) was observed in 10 of 41 samples (24%) and in 11 of 41 samples (27%), respectively. Loss of expression of proapoptotic proteins was observed as follows: Bak, 24 of 41 samples (59%); Bad, 21 of 41 samples (51%); Bid, 20 of 41 samples (49%); Bax, 14 of 41 samples (34%); and Bim/Bod, 2 of 41 samples (5%). Statistically significant differences in expression between adenocarcinoma samples and squamous cell carcinoma samples were observed for Bcl-X(L) (overexpression in 11 of 19 adenocarcinomas [58%] vs. 0 of 22 squamous cell carcinomas [0%]; P < 0.001) and for Bad (loss of expression in 5 of 19 adenocarcinomas [26%] vs. 16 of 22 squamous cell carcinomas [73%]; P = 0.004). CONCLUSIONS: Although this was only a pilot study, the results revealed significant differences in the expression of apoptosis-related proteins both between individual samples of nonsmall cell lung carcinoma and between the two main histologic subtypes. Such differences may play a role in the development of lung tumors; and, if it is found that these differences are of clinical importance, then it may be required to regard nonsmall cell lung carcinoma subtypes as separate entities rather than as one disease.     

Survivin in esophageal cancer: An accurate prognostic marker for squamous cell carcinoma but not adenocarcinoma

We quantified the expression of survivin, both as mRNA in real-time PCR and protein in immunohistochemistry, in tumor samples of 112 patients with esophageal cancer (56 squamous cell carcinomas and 56 adenocarcinomas). Overall survival of squamous cell carcinoma patients with high survivin mRNA levels was significantly less than that of patients with low survivin mRNA levels (p = 0.0033). Distribution pattern of survivin (nuclear vs. cytoplasmic or mixed) was not correlated to survival, while the extent of immunostaining was significantly correlated to survivin mRNA values (p = 0.016) and had prognostic relevance in univariate analysis (p = 0.0012). Cox's proportional-hazard regression model showed that tumor survivin expression in esophageal squamous cell carcinoma was the most important prognostic factor, independent of tumor stage and other histopathological factors, both as mRNA relative value (p = 0.0259) and protein immunostaining (p = 0.0147). In esophageal adenocarcinoma, survivin expression and pattern of distribution had no prognostic relevance. Thus, quantifying survivin expression provides a prognostic marker only for esophageal squamous tumors.     

Immunohistological study of cell cycle-related factors,oncogene expression,and cell proliferation in adenocarcinoma developed in Barrett's esophagus

In addition to presenting clinicopathological findings in 3 patients with adenocarcinoma developed in Barrett's esophagus, we have investigated the expression of cell cycle-related factors, oncogenes and cell proliferation in normal squamous epithelium, specialized columnar epithelium (SCE) and adenocarcinoma in Barrett's esophagus, using immunohistological techniques. The expression of p21 in adenocarcinoma in Barrett's esophagus tended to be decreased in two mutated p53-strongly-positive patients and to be increased in one mutated p53-weakly-positive patient. Furthermore, mutated p53 was strongly expressed in the deep layer of the cancer, while p21 was expressed in the superficial layer of the cancer. Thus, mutated p53 was inversely correlated with p21 in adenocarcinoma in Barrett's esophagus. The mean positive cell rate (PR) of Ki-67 was 4% in normal squamous epithelium, 24.5% in the SCE, and 41.7% in the adenocarcinoma in Barrett's esophagus. The mean PR of proliferating cell nuclear antigen (PCNA) was 6% in normal squamous epithelium, 29.5% in the SCE, and 55% in the adenocarcinoma in Barrett's esophagus. Thus, the PR of Ki-67 and PCNA were clearly higher in the SCE in Barrett's esophagus than in normal squamous epithelium, indicating increased cell proliferation in the SCE in Barrett's esophagus. In conclusion, mutated p53 was inversely correlated with p21 in adenocarcinoma in Barrett's esophagus. p53 mutation and the expression of oncogenes such as c-erbB-2 and MDM2 were observed in the SCE in Barrett's esophagus, which showed higher cell proliferation than normal squamous epithelium, suggesting a high malignant potential of the SCE in Barrett's esophagus. We considered that it was important to carefully follow-up patients with Barrett's esophagus.     

Deletion mapping on the short arm of chromosome 3 in squamous cell carcinoma and adenocarcinoma of the lung.

We examined loss of heterozygosity in 49 adenocarcinomas and 18 squamous cell carcinomas of the lung with 19 RFLP markers on the short arm of chromosome 3. Although no interstitial deletions were observed in any squamous cell carcinomas, interstitial or partial deletions were detected in 23 adenocarcinomas. Identification of two common regions of deletion in adenocarcinomas, at 3p21.3 and 3p14.1-21.1, suggested the presence of at least two tumor suppressor genes on 3p within the same regions commonly deleted in renal cell carcinomas. Correlation between the frequency of loss of heterozygosity on 3p and histopathological grade of adenocarcinoma also was observed. These results imply an etiological difference between two major types of non-small cell lung cancers, adenocarcinoma and squamous cell carcinoma.     

WWOX expression in different histologic types and subtypes of non-small cell lung cancer.

PURPOSE: Non-small cell lung cancer (NSCLC) has heterogeneous histopathologic classification and clinical behavior and very low survival rate. WWOX (WW domain-containing oxidoreductase) is a tumor suppressor gene, and its expression is altered in several cancers. The purpose of this study is to better define the role of WWOX in NSCLC tumorigenesis and progression by determining its pathogenetic and prognostic significance. EXPERIMENTAL DESIGN: WWOX protein expression was evaluated by immunohistochemistry in 170 patients with NSCLC (101 squamous cell carcinomas, 66 adenocarcinomas, 3 large cell carcinomas) and was correlated with histopathologic (histotype, subtype, grade, tumor-node-metastasis, stage, index of cell proliferation Ki67/MIB1) and clinical (age, gender, local recurrences, distant metastases, overall survival, and disease-free survival) characteristics. RESULTS: WWOX expression was absent/reduced in 84.9% of NSCLCs, whereas it was normal in 80.5% of adjacent normal lung tissues. WWOX expression was strongly associated with tumor histology (P=1.1x10(-5)) and histologic grade (P=0.0081): the percentage of cases with absent/strongly reduced WWOX expression was higher in squamous cell carcinomas and in poorly differentiated tumors. Regarding adenocarcinoma, bronchioloalveolar pattern showed normal WWOX expression in 62.5% of the cases, whereas in solid and acinar patterns, a prevalence of cases with absent/very low WWOX expression was observed (79.2% and 50%, respectively). Finally, weak WWOX staining intensity was related to the high index of cell proliferation (P=0.0012). CONCLUSIONS: Our results suggest that the loss of WWOX expression plays different roles in tumorigenesis of distinct histotypes and subtypes of NSCLC and is related to high aggressiveness (G3; high proliferating activity) of tumors.     

Expression of ras oncogene p21 protein in relation to regional spread of human breast carcinomas

The oncogenes most frequently detected in human tumors belong to the ras gene family (Ha-ras, Ki-ras, and N-ras). These genes encode a group of closely related 21,000 dalton proteins termed p21. An immunohistochemical study of ras p21 expression was carried out on paraffin sections of 54 human breast carcinomas using monoclonal antibodies to p21. The control group consisted of ten cases of benign fibrocystic disease. The p21 expression was significantly higher in cancer cells than in epithelial cells of control specimens. No correlations, however, were observed between oncogene product expression and tumor size, histologic type, or grade. As a group, tumors with axillary lymph node metastases expressed higher levels of ras p21 than nonmetastasizing tumors. However, because of the significant overlap in individual p21 values, it is unlikely that the immunohistochemical assay for p21 could be used to predict the behavior of mammary carcinomas.