Overexpression of C-fos and C-erbb1 encoded proteins in squamous-cell carcinomas of the lung of smokers

Seventy-eight human squamous cell carcinomas of the lung of previously untreated patients were analyzed for expression of c-fos and c-erbB1 proteins by means of immunohistochemistry. Of the tumors investigated expression of c-fos protein was detected in 60% and of c-erbB1 protein in 77%. Carcinomas of smokers significantly express more frequently c-fos and c-erbB1 protein than carcinomas of non-smokers (p<0.05).     

非小细胞肺癌组织p53和c-erbB2及MRP蛋白的表达

目的探讨癌组织p53、c-erbB2、MRP蛋白表达与非小细胞肺癌（NSCLC）临床病理特征的关系及其预后评估意义。方法应用免疫组织化学方法检测NSCLC患者的肺组织切除标本p53、c-erbB2、MRP蛋白表达,并与其临床病理参数进行比较分析。结果NSCLC组织p53、c-erbB2、MRP蛋白表达阳性率分别为53.9%（82/152）、44.1%（67/152）及43.4%（66/152）。p53表达与性别、细胞分化程度、临床分期、淋巴结转移有显著关系（P〈0.05）,而c-erbB2与各因素间无统计学差异,肺腺癌MRP蛋白表达阳性率（67.6%）明显高于肺鳞癌（33.0%）,有统计学差异（P〈0.05）。癌组织p53、c-erbB2、MRP 3种蛋白表达均阳性者的1、2、3年生存率明显低于均阴性者（分别P=0.02、0.01和0.00）,p53、c-erbB2、MRP蛋白表达阳性者单纯手术后生存率也明显低于阴性者（P〈0.05）;p53、c-erbB2、MRP 3种蛋白表达均阴性者预后最好,1-2种阳性者次之,3种均阳性者预后最差（P〈0.05）。术后辅助化疗组MRP、c-erbB2蛋白表达阳性者的生存率低于阴性者（P〈0.01）,但p53蛋白表达阳性与阴性患者的生存率无统计学差异（P=0.82）;MRP与c-erbB2表达双阴性者生存率显著高于双阳性者,MRP或c-erbB2单一阳性的生存率介于前两者之间（P=0.01）。多因素Cox分析显示细胞分化程度、c-erbB2是影响NSCLC患者疗效和预后的独立预测因子。结论肿瘤组织p53、c-erbB2、MRP 3种蛋白同时高表达的NSCLC病例预后较差。术后检测p53、c-erbB2、MRP表达对评估可手术NSCLC患者疗效和预后有一定意义。     

Expression of c-erbB2 and p53 protein is similar in breast cancer from British and Japanese women.

In an attempt to explain the difference in outcome between British and Japanese women with breast cancer we have compared histopathological features, expression of c-erbB2 and p53 proteins and clinical outcome of 191 British (Anglo) women with 171 Japanese women treated between 1979 and 1980. The Japanese patients were significantly younger than the Anglo patients, while in premenopausal women the latter had significantly smaller tumors. The proportion of tumors expressing c-erbB2 and p53 proteins was similar in both populations. c-erbB2 positivity was significantly associated with positive lymph node status and with poorly differentiated carcinomas. Duration of relapse-free and overall survival was significantly longer in the Japanese women than in the Anglo women. Women with c-erbB2-negative tumors had a longer overall survival than women with c-erbB2-positive tumors and this difference was accentuated when patients were stratified according to country of origin. Japanese women with c-erbB2-negative tumors had the best outcome, whereas the Anglo women with c-erbB2-positive tumors had the worst. There was no relationship between p53 status and any histopathological features or clinical outcome. Differences in the expression of c-erbB2 and p53 do not explain the better outcome experienced by Japanese breast cancer patients.     

老年宫颈癌p53和c-erbB2表达及其临床意义

背景与目的：老年宫颈癌分子生物学方面的研究尚不多见,因此我们将探讨抑癌基因p53和癌基因c-erbB2表达在其发生发展过程中的意义。方法：应用免疫组化LSAB法检测79例老年宫颈癌及23例正常老年宫颈上皮石蜡切片的p53和c-erbB2蛋白阳性率。结果：老年宫颈浸润癌和正常宫颈上皮p53蛋白阳性率分别为18．98％和0（P＜0．01）,而c-erbB2表达率为43．04％和34．78％（P＝0．63）。组织学分级I、Ⅱ、Ⅲ级中p53蛋白阳性率分别为50．00％、11．76％和17．14％（P＝0．01）,c-erbB2表达率分别为80．00％、38．24％及37．14％（P＜0．01）。临床分期I、Ⅱ、Ⅲ／Ⅳ期中p53表达分别为11．11％、15．38％、25．18％（P＝0．26）,c-erbB2蛋白阳性率为33．33％、38．46％和51．61％（P＜0．01）。淋巴结无转移组及转移组p53蛋白阳性率为6．67％、41．67％（P＝0．01）,c-erbB2表达率为26．67％、58．33％（P＝0．08）。结论：p53蛋白在老年宫颈癌发生发展中可能起作用,它可能是预测淋巴结转移的重要指标。c-erbB2基因过度表达可能是老年宫颈癌发生的早期事件。     

Quantitation of biological tumor markers (p53, c-myc, Ki-67 and DNA ploidy) by multiparameter flow cytometry in non-small-cell lung cancer.

Fifteen primary non-small-cell lung carcinomas (8 adenocarcinomas and 7 squamous-cell carcinomas) were analyzed by multiparameter flow cytometry for their expression of p53 and c-myc proteins. In addition, the fraction of cells staining with the proliferation-associated antibody Ki-67 and DNA ploidy was determined. These 4 biological markers were analyzed in parallel samples from a single-cell suspension made from fresh, frozen biopsies. Thus, the internal relationship between these markers within each tumor-cell population was established. Three different anti-p53 antibodies were used: PAb 421, PAb 1801 and PAb 240. All 15 tumors were p53-positive with the antibodies PAb 1801 and PAb 240, whereas only 9 were positive as judged by the antibody PAb 421. This indicates that the choice of p53 antibody is not irrelevant. Ten tumors were c-myc-positive; 7 of these were adenocarcinomas. The c-myc-positive tumors had a significantly higher level of p53 expression, judged by PAb 1801 and PAb 240, than c-myc-negative tumors. For PAb 421, there was no difference. We did not find any correlation between Ki-67 staining and expression of p53 and c-myc proteins, either with DNA ploidy, S-phase fraction or histological type. Our study indicates that there might be an association between accumulation of p53 protein and c-myc over-expression in non-small-cell lung cancer, and that this in particular might apply to adenocarcinomas. Furthermore, we show that multiparameter flow cytometry is a powerful tool in the study of the relationship between different markers in a cell population.     

Expression of c-erbB3 protein in primary breast carcinomas.

Expression of c-erbB3 protein was investigated in 104 primary breast carcinomas comprising nine comedo ductal carcinoma in situ (DCIS), 91 invasive ductal carcinomas and four invasive lobular carcinomas using two monoclonal antibodies, RTJ1 and RTJ2. Of the 91 invasive ductal carcinomas, seven contained the comedo DCIS component adjacent to the invasive component. An immunohistochemical technique was used to evaluate the association between expression of c-erbB3 and clinical parameters and tumour markers such as epidermal growth factor receptor (EGFR), c-erbB2, cathepsin-D and p53 in archival formalin-fixed paraffin-embedded tumour tissues. Our results indicated that RTJ1 and RTJ2 gave identical staining patterns and concordant results. It was found that the overexpression of c-erbB3 protein was observed in 67% (6/9) of comedo DCIS, 52% (44/84) of invasive ductal carcinomas, 71% (5/7) of carcinomas containing both the in situ and invasive lesions and 25% (1/4) of invasive lobular carcinomas. A significant relationship (P < 0.05) was observed between strong immunoreactivity of c-erbB3 protein and histological grade, EGFR and cathepsin-D, but not with expression of c-erbB2, p53, oestrogen receptor status, lymph node metastases or age of patient. However, we noted that a high percentage of oestrogen receptor-negative tumours (59%), lymph node-positive tumours (63%) and c-erbB2 (63%) were strongly positive for c-erbB3 protein. We have also documented that a high percentage of EGFR (67%), c-erbB2 (67%), p53 (75%) and cathepsin-D-positive DCIS (60%) were strongly positive for c-erbB3. These observations suggest that overexpression of c-erbB3 protein could play an important role in tumour progression from non-invasive to invasive and, also, that it may have the potential to be used as a marker for poor prognosis of breast cancer.     

Prognostic value of oncoproteins for the survival of patients with nonsmall cell lung carcinomas

Patients with non-small cell lung carcinomas whose tumors showed an overexpression of the oncogenes c-fos and c-N-ras at the protein level had significantly shorter survival times than those without overexpression of these oncogene products. (c-fos: p=0.0002, c-N-ras: p=0.002). Multivariate analysis showed that expression of proteins coded by c-fos and c-N-ras is a significant prognostic factor in addition to tumor staging and DNA ploidy. The prognostic value is improved by combining the expression of c-fos and c-N-ras products. A significant correlation between the expression of c-fos and c-N-ras products and the tumor take rate in nude mice was found.     

Coexpression of cyclin D1 and retinoblastoma gene product (pRb) in human squamous cell lung carcinomas is associated with increased tumor take rate in nude mice

Samples from 72 squamous cell lung carcinomas were analyzed immunohistochemically for the expression of cyclin D1 and pRb. Expression of cyclin D1 was found in 61% and expression of pRb in 39% of the cases. The take rate of human squamous cell lung carcinomas in nude mice was significantly different according to the expression of cyclin D1 and expression of pRb in primary human tumors [cyclin D1-negative (32%) vs. cyclin D1-positive (59%); P=0.026; pRb-negative (34%) vs. pRb-positive (71%); P=0.002]. The take rate was improved by coexpression of both proteins [both proteins negative/both proteins positive: 12% vs. 80% (P=0.00005)]. An association of the take rate and clinical parameters (age, extent of tumors, lymph node involvement, stage) could not be observed. Coexpression of cyclin D1 and pRb is also a prognostic factor for the patients' survival.     

Human papilloma virus and p53 expression in bladder cancer in Egypt: Relationship to schistosomiasis and clinicopathologic factors

The aim of the current study was to compare the role of p53 and human papillomavirus (HPV) in schistosomiasis-related and schistosomiasis-unrelated carcinoma of the urinary bladder. To achieve this aim, we investigated 114 bladder carcinomas for p53 oncoprotein expression by immunohistochemistry and for human papillomavirus by in situ hybridization technique. The results revealed that 64 tumors (56.1%) were schistosomiasis-associated. Sixty seven (58.8%) were transitional cell carcinomas and 32 (28%) were squamous cell carcinomas. The remaining 15 tumors (13.2%) included adenocarcinomas and sarcomatoid carcinomas. In both schistosomiasis-associated and non-associated carcinomas, p53 oncoprotein expression was significantly higher in poorly differentiated tumors. However, it was significantly higher in locally more invasive tumors in the schistosomal carcinomas only. HPV types 16/18 could be detected in 1 of the 114 bladder carcinomas (0.95%), which was schistosomiasis-related squamous cell carcinoma in situ. These results suggest that p53 immunohistochemistry can be a prognostic factor in both schistosomal and nonschistosomal bladder cancer. More importantly, HPV does not seem to play a role in the pathogenesis of either type of bladder cancer in our country.(Pathology Oncology Research Vol 12, No 3, 173–178) An erratum to this article is available at .     

Abnormal expression of pan-ras, c-myc and tp53 in squamous cell carcinoma of cervix: correlation with HPV and prognosis

The aim of this study is to assess, in squamous cell carcinoma of the cervix, the expression of pan-ras, c-myc and tp53 at protein level using an immunohistochemical (IHC) staining method. One hundred and seven patients with squamous cell carcinoma of the cervix were recruited. Fifty-four patients were of stage 1B/2A and 53 were of stage 2B and above. Positive IHC stainings of pan-ras, c-myc and tp53 proteins were detected in 80.4%, 32.7% and 25.2% of cases, respectively. No significant correlation between overexpression of pan-ras and c-myc was detected. However, significantly higher percentages of overexpression of c-myc was found in association with overly expressed tp53 samples (p = 0.014). Human papillomavirus (HPV) was detected in 77.6% of cancers. HPV 16/18 was detected in 72% of cancers. Overexpression of pan-ras and c-myc had no correlation with HPV detection and stage. However, higher percentages of overexpression of tp53 were found in early stage disease (p = 0.017) and in HPV 16/18 positive tumors (p = 0.006). Overexpression of pan-ras, c-myc and tp53 alone or in more than one oncogenes had no prognostic significance on survival.     

Differences in Ki67 and c-erbB2 expression between screen-detected and true interval breast cancers.

Breast cancer screening facilitates the early detection of breast cancer, although a significant number of tumors still arise in the interval between screening. The objective of this study was to measure the expression of five markers of proven prognostic significance in symptomatic breast cancer (estrogen receptor, progesterone receptor, p53, Ki67, and c-erbB2) in screen-detected and interval breast cancers to identify biological markers that may be associated with the emergence of symptomatic breast cancer in the screening interval. The expression of estrogen receptor, progesterone receptor, p53, Ki67, and c-erbB2 was assessed in a series of 51 true interval and 84 screened-detected invasive tumors by immunohistochemistry. Interval cancers tended to be of higher histological grade and were of larger pathological size than screen-detected cancers. Expression of estrogen receptor was 1.7-fold lower (P<0.001), whereas expression of p53 was 2.5-fold (P<0.01), Ki67 2.4-fold (P<0.001), and c-erbB2 3.6-fold higher (P<0.01) in true interval cancers compared with screen-detected invasive cancers. There was no significant difference in progesterone receptor expression. The most important differences identified by multiple logistic regression analysis were in the expression of Ki67 and c-erbB2. The differences in the expression of these markers were more important than clinical features such as pathological grade and size. Using the logistic regression model, 83% of the tumors analyzed in this study could be correctly assigned as interval or screen-detected tumors on the basis of Ki67 and c-erbB2 expression. The importance of high expression of Ki67 in interval cancers compared with screen-detected cancers suggests that tumors may become symptomatic in the screening interval as a result of increased levels of cell proliferation. The inclusion of c-erbB2 in the regression equation suggests that this growth factor receptor may play a significant role in stimulating the rapid growth of interval cancers.     

癌蛋白c—erbB2在乳腺肿瘤患者中过度表达的免疫组化研究

目的检测ｃ－ｅｒｂＢ２蛋白过度表达与乳腺肿瘤患者预后的关系,探讨其作为预后指标的可行性。方法共８５例原发乳腺肿瘤的石蜡切片标本,采用免疫组化方法。结果７例良性病变无１例过度表达;７８例乳腺癌２３例过度表达,表达率为２９．４％;８０％的无淋巴结转移病例未检测到ｃ－ｅｒｂＢ２的过度表达。ｃ－ｅｒｂＢ２蛋白的过度表达在临床Ⅲ期病例中占７１％。ｃ－ｅｒｂＢ２与雌激素受体（ＥＲ）表达呈相反关系的占６７％。该蛋白过度表达与腋淋巴结转移情况未发现相关性（Ｐ＞０．０５）,与临床分期呈显著的正相关（Ｐ＜０．００５）,与ＥＲ呈显著的负相关（Ｐ＜０．００５）。结论ｃ－ｅｒｂＢ２过度表达者预后不良。它可以作为判断乳腺肿瘤患者预后的有效指标,用于临床,辅助判断患者预后,可能具有重要意义。     

Predictive value of topoisomerase IIalpha and other prognostic factors for epirubicin chemotherapy in advanced breast cancer.

Although cytotoxic chemotherapy is widely used in advanced breast cancer, there are no powerful predictors for the therapy response. Because topoisomerase IIalpha (Topo IIalpha) is the molecular target for the anthracycline class of anti-cancer drugs, we compared the immunocytochemical assay of Topo IIalpha with other biomarkers in the prediction of clinical response to Topo II inhibitor chemotherapy. Fifty-five patients with advanced breast cancer were treated with a single cytotoxic drug, Topo II-inhibitor, epirubicin (30 mg m(-2) weekly up to 1000 mg m(-2)), as first line cytotoxic chemotherapy. Objective response to treatment was analysed according to UICC criteria. The predictive value of Topo IIalpha expression, c-erbB2 oncoprotein, p53 tumour-suppressor protein, oestrogen (ER) and progesterone receptor (PR), S-phase fraction and DNA ploidy were analysed from representative formalin-fixed paraffin-embedded primary tumour samples. The proportion of Topo IIalpha-positive cells (Topo IIalpha index) failed to predict response to epirubicin therapy. Mean Topo IIalpha scores in 29 responding patients were similar when compared with those with no change in disease progression (n = 13) and those with progressive disease (n = 13) (14.9% +/- 11.4% vs 15.5% +/- 7.6% vs 17.3% +/- 13.2%, not significant). Among the other biomarkers tested, overexpression of c-erbB2 oncoprotein and hormone receptor negativity were significantly associated with poor response. Response rate in patients with c-erbB2-overexpressing tumours was 32% compared with 65% in patients with no c-erbB2 overexpression (P = 0.0058). Accordingly, the response rate for ER-positive patients was 67% compared with 26% in ER-negative patients (P = 0.0021). Although both negative ER status and c-erbB2 overexpression are associated with high Topo IIalpha expression in breast cancer, step-wise logistic regression analysis showed that ER and c-erbB2 were associated with therapy response independent of Topo IIalpha expression. Histological grade, p53, DNA-ploidy, tumour proliferation rate (S-phase fraction), stage of the disease at diagnosis, age of the patient, previous anti-oestrogen therapy or site of metastasis did not predict the response to epirubicin therapy. In conclusion, despite extensive in vitro evidence, expression of Topo IIalpha is unlikely to predict the response to Topo II inhibitor chemotherapy in advanced breast cancer. Among the prognostic biomarkers, overexpression of c-erbB2 oncogene and negative ER may have predictive value in epirubicin therapy in patients with advanced breast cancer.     

Expression of c-Myc, c-Fos, and c-jun in hepatocellular carcinoma

BACKGROUND: Increased expression of the proto-oncogene c-myc is a common phenomenon in hepatocellular carcinoma (HCC). The proto-oncogenes c-fos and c-jun are involved in cell cycle progression and cellular proliferation. METHODS: The objective of this study was to elucidate the mechanism of hepatocarcinogenesis with regard to the expressions of c-myc, c-fos, and c-jun. One hundred fifty biopsied HCC specimens were stained immunohistochemically for the above phenotypic markers both in tumor tissue and in adjacent nontumor tissue. RESULTS: Although the expression of c-myc was high (74%) in tumor tissue, it was significantly less compared with the expression in nontumor tissue (100%; P = 0.0002). The expression of c-myc was inversely proportional to the grade of differentiation in tumor tissue (P = 0.0108; correlation coefficient [r] = -0.244); that is, tissue with poorer histologic differentiation had a lower level of c-myc expression. There were inverse associations between the expression of c-myc and the expression of mutated p53 (P = 0.0017; r = -0.285) as well as the expression of Ki67 (P = 0.057; r = -0.147). There was significantly high expression of c-fos in tumor tissue compared with the expression in nontumor tissue (91% vs. 0%; P < 0.0001). Both the tumor tissue and the nontumor tissue had high levels of expression of c-jun (96.53% and 100%, respectively). There was a trend toward a positive association between the expression of c-fos and the expression of c-jun in tumor tissue (P = 0.07; r = 0.162). CONCLUSIONS: Because c-myc is a known inducer of wild type p53, decreased c-myc expression may lead to uncontrolled cell growth because of the lack of p53 expression that normally induces apoptosis. The coordinated expression of c-fos and c-jun in HCC may reflect the coordinated tumor cell cycle of progression and proliferation; however, future studies are required to elucidate this possibility.     

284例原发乳腺癌c-erbB2蛋白的表达及其与预后的关系

目的探讨c-erbB2癌蛋白在原发乳腺癌组织中的表达情况及其与预后的关系。方法采用免疫组化SP法检测284例原发乳腺癌组织的c-erbB2表达,并用统计学分析其与预后的关系。结果284例原发乳腺癌c-erbB2的阳性表达率为26．8％（76／284）,其表达与淋巴结转移数目（P=0．003）密切相关。单因素分析表明,c-erbB2是总生存时间（OS,P=0．002）和无病生存时间（DFS,P=0．024）的重要预后因素;多因素分析表明,c-erbB2是影响Os（P=0．023）的独立预后因素。此外,c-erbB2阳性的肿瘤患者较阴性者更易于发生内脏转移。而对于不同的淋巴结转移和ER状态,c-erbB2也有不同的预后价值。结论c-erbB2是影响原发乳腺癌患者OS的独立因素;在不同的淋巴结转移和ER状态下,其预后价值不同。     

Oncoprotein changes in the flat lesions with atypia and invasive neoplasms of the urinary bladder

We analyzed six cystectomized specimens diagnosed as transitional cell carcinoma by immunohistochemical evaluation to determine the presence of c-erbB2, transforming growth factor-alpha (TGF-alpha), c-myc, c-fos, and c-fms. Representative sections of flat lesions with atypia (e.g., reactive atypia, dysplasia, and carcinoma in situ) and invasive neoplasms (transitional cell carcinoma, TCC) were selected for each cystectomy specimen according to the new WHO/ISUP classification. The average percentage of cells found positive for c-erbB2 were 16.3%, 45.5%, 46.1% and 67.7% in the reactive atypia, dysplasia, carcinoma in situ, and invasive TCC, respectively. The average percentage of cells found positive for TGF-alpha were 9.7%, 13.3%, 13.5%, 30.3%, respectively. The cells were negative for the oncoproteins c-myc and c-fos. The average percentage of cells found positive for the oncoprotein c-fms was 10.6%, 15.5%, 16.7%, and 45.5% respectively. The results of this study indicated that various oncoproteins are expressed differently. c-erbB2, TGF-alpha and c-fms expression was gradually increased during tumorous progression of the urothelium from reactive atypia to invasive carcinoma. The presence of c-erbB2, TGF-alpha and c-fms is an important marker for detection of an early precursor lesions of invasive carcinoma. However, c-myc and c-fos were not expressed in the urothelial reactive atypia and dysplasia and did not correlate with tumor progression.     

Bcl-2 expression in non-small cell lung cancers: higher frequency of expression in squamous cell carcinomas with earlier pT status

Abnormal expression of the bcl-2 gene product (Bcl-2) has been found in a wide variety of tumors, including lung cancer. In the present study, a total of 116 tumor specimens from surgically resected non-small cell lung cancer (NSCLC) patients, that were previously studied for p53 protein expression, were analyzed with immunohistochemistry for Bcl-2 expression. Forty (34%) of 116 tumor specimens showed Bcl-2 expression, which was found to occur more frequently in males than females (p = 0.049) and to be associated with smoking (p = 0.047). Bcl-2 expression was more frequently observed in squamous cell carcinomas (27 of 51, 53%) than in adenocarcinomas (12 of 55, 22%; p = 0.002), and in pT1 tumors (11 of 13, 85%) than in pT2 and pT3 tumors (16 of 38, 42%) in squamous cell carcinomas (p = 0.01). Bcl-2 expression did not correlate either with p53 protein status. We compared Bcl-2 expression in primary tumors and metastatic tumors of regional lymph nodes. Of 11 cases with Bcl-2-negative primary tumors, 10 were Bcl-2-negative in metastatic tumors except 1 case. In contrast, of 10 cases with Bcl-2-positive primary tumors, 6 lost Bcl-2 expression in metastatic tumors, while the remaining 4 cases still showed Bcl-2 expression in metastatic tumors. In the 89 potentially curatively treated patients, those with Bcl-2-positive and Bcl-2-negative tumors did not show a significant difference in survival (5-year survival rates, 56 and 42%, respectively, p = 0.2 by the generalized Wilcoxon test). These data indicate that Bcl-2 expression is frequently observed in squamous cell carcinomas with early pT status, and that it does not predict prognosis of patients with NSCLC.     

Proliferative (mib1, mdm2) versus anti-proliferative (p53) markers in head and neck cancer. An Immunohistochemical study

Formalin fixed and paraffin embedded samples from 36 squamous cell carcinomas of the larynx and the oral cavity (pT₂N₀M₀, R₀) surrounded by non-tumorous mucosa were studied immunohistochemically using a panel of four different anti-p53 antibodies (CM1, PAbl801, D07, PAb240), a monoclonal anti-mdm2 antibody and MIB1, following wet autoclave antigen retrieval. P53 immunoreactivity was detected in 11/14 laryngeal and in 9/22 oral carcinomas. All p53 positive oral, and all but one laryngeal tumors revealed mdm2 positivity as well, whereas in p53 negative tumors 4/12 and 1/3 mdm2 immunopositive cases were demonstrated, respectively. MIB1 labeling indices of the tumors ranged between 18% – 64% in p53 positive cases, and 10% – 53% in p53 negative ones. The difference was not statistically significant. Close spatial coexpression of p53, mdm2 and MIB1 immunoreactivity was observed at the invasive front of the carcinomas and in the basal and suprabasal layers of the non-tumorous epithelium in all p53 positive cases. However, the MIB1 expression was similarly increased at the invasive margins in carcinomas lacking immunohistochemically detectable p53 alterations. Our results strongly suggest that p53 overexpression does not necessarily correspond to increased rate of proliferation, but rather to mdm2 overexpression and is largely dependent on the anatomical site in case of small and localized squamous cell carcinomas of the head and neck region.     

Clinical significance of c-myc and p53 expression in head and neck squamous cell carcinomas

c-myc and p53 genes were frequently deregulated in head and neck squamous cell carcinoma (HNSCC). To determine if the concomitant expression of the two oncogenes might have prognostic value, the survival and free disease time of 140 consecutive HNSCC patients followed up for a median time of 29.9 months was analyzed in the light of p53 and c-myc expression assessed by immunohistochemistry. Positive c-myc and p53 staining was detected respectively in 35.7 and 50.7% of the tumors. Double positivity emerged in 16.4% of the cases. Overall-survival of patients was not associated with the immunoreactivity of p53 or c-myc considered separately or grouped in subsets. Considering only the advanced stages, the concomitant expression of both oncogenes in tumors was associated with worse disease-free survival (P = 0.004) suggesting a role for p53 and c-myc genes in progression of this HNSCC subset. Clinical parameters (presence of lymph nodes, histologic grade and tumor width) remained important indicators of overall survival (OS).