Role of squamous cell carcinoma antigen 1 expression in the invasive potential of head and neck squamous cell carcinoma

BACKGROUND: Serine proteases have important roles in tumor invasion and metastasis, and their inhibitors, serine protease inhibitors (serpins), are attractive targets for therapeutic strategies. On chromosome 18q21, there is a cluster of serpins: maspin, headpin, and squamous cell carcinoma antigen 1 (SCCA1)/SCCA2. Others and we have reported that the expression of these serpins is down regulated in head and neck squamous cell carcinoma (HNSCC) cells compared with normal squamous epithelial cells. In this study, we hypothesized that expression of SCCA1 is biologically disadvantageous to HNSCC cells. METHODS: HNSCC cell lines were transfected with a mammalian expression vector with SCCA1 cDNA. In vitro proliferation, migration, or invasive potential (matrigel assay) of the transfectants were assayed. In addition, the in vivo growth and invasion was analyzed using the floor-of-mouth model of nude mice. RESULTS: SCCA1 expression did not alter the in vitro growth rate of established HNSCC cells. However, SCCA1 expression significantly inhibited the in vitro invasion in matrigel assays. Furthermore, the in vivo growth and invasion in nude mice was also inhibited by SCCA1 expression. CONCLUSIONS: Overexpression of SCCA1 in a HNSCC cell line inhibited its invasive potential. Loss of expression of the serpin SCCA1 may play a role in the malignant progression of HNSCC.     

Autologous anticancer antigen preparation for specific immunotherapy in advanced renal cell carcinoma

33 patients with metastatic renal cell carcinoma were treated intradermally with an autologous (29 patients) or allogeneic (4 patients) irradiated tumor cell preparation mixed with Corynebacterium parvum given monthly after palliative nephrectomy (27 patients) or excision of tumor metastases (2 patients). No significant toxicity was produced. 8 patients (24%) underwent objective responses. Responding patients had a median survival of 32 months, the median survival of all patients was 17 months (differences not significant).     

Clinical and fundamental study of a squamous cell carcinoma related antigen (SCC-RA) for esophageal squamous cell carcinoma

SCC-RA is one of the fractions of TA-4, extracted and purified from uterine cervical squamous cell carcinoma. I studied SCC-RA in order to evaluate its significance as a tumor marker for esophageal carcinoma. In 32 of 75 (42.7%) esophageal cancer patients, serum SCC-RA was positive. As compared with IAP and CEA, SCC-RA was the best marker to monitor esophageal cancer. SCC-RA positive patients tended to die earlier than negative ones, and it was considered to be one of the prognostic factors. In the immunohistochemical study using anti SCC-RA monoclonal antibody, both the normal epithelium and the carcinoma tissue reacted with SCC-RA. In the carcinoma tissue. SCC-RA reactivity was observed in 27 of 31 specimens (87%). However there was no correlation among the reactivity, the serum level and clinical stage. Furthermore, I studied the relationship between the tumor growth and the serum SCC-RA levels in the nude mice bearing human esophageal squamous cell carcinoma xenografts. The SCC-RA levels in mice sera gradually increased and they correlated well to the tumor volume. In conclusion, SCC-RA reflected the tumor volume and clinical stage, and SCC-RA is useful for monitoring esophageal cancer patients.     

细胞因子对肾癌特异抗原G250表达的影响

目的 研究细胞因子对肾癌细胞特异性抗原G250表达的影响。方法 单独或联合应用不同浓度的白细胞介素（IL）-2、干扰素（IFN）-α、IFN-γ刺激肾癌786-0细胞系，刺激24、48、96h后，运用免疫组织化学、Western blot和逆转录-聚合酶链反应（RT-PCR）技术检测G250抗原在肾癌786旬细胞上的表达。结果 IL-2、IFN-α、IFN-γ均能上调786-0细胞G250抗原表达，以IFN-γ作用最强，上调作用具有浓度及时间依赖性。细胞因子联用能明显增强G250抗原表达的上调作用。结论 IL-2、IFN-α、IFN-γ能上调肾癌786-0细胞G250抗原表达，联合应用效果更大。提示细胞因子联合以G250抗原为靶点的免疫治疗有望成为晚期肾癌新的治疗途径。     

Nuclear and cytoplasmic p53 expression in pharyngeal squamous cell carcinoma: prognostic implications

BACKGROUND: The role of p53 expression in human neoplasms is still controversial, and it has been associated with both favorable and unfavorable outcome of the patients. Also cytoplasmic expression of p53 protein has been reported to affect survival in some cancers. Furthermore, an association between p53 and beta-catenin expression has been demonstrated. We studied the expression of p53 in a large group of oropharyngeal and hypopharyngeal squamous cell carcinomas and its relation to catenin expression, histologic differentiation, clinical data, and prognosis. METHODS: Primary tumors for analyses were obtained from 123 patients diagnosed with squamous cell carcinoma of the oropharynx or hypopharynx between 1975 and 1998 in Eastern Finland. Immunohistochemistry was used to evaluate the expression of p53 as well as alpha-, beta-, and gamma-catenins. RESULTS: In the primary tumors (n = 123), the nuclear p53 expression index was low in 42 (34%), intermediate in 38 (31%), and high in 43 (35%) cases. Cytoplasmic p53 expression was present in 56 (46%) and absent in 67 (54%) tumors. In univariate analyses (Kaplan-Meier), hypopharyngeal primary site (p =.02), high T class (p <.0005), presence of distant metastases (p =.02), low Karnofsky performance index (p <.0005), high nuclear p53 expression index (p =.01), and positive cytoplasmic p53 expression (p =.04) predicted poorer overall survival (OS). In Cox proportional hazards model, only T class (p =.0005), Karnofsky performance index (p =.005), and nuclear beta-catenin expression (p =.038) predicted poorer OS. CONCLUSION: Positive cytoplasmic p53 expression and nuclear p53 overexpression seem to relate to more aggressive features and unfavorable outcome in pharyngeal squamous cell carcinoma (PSCC). However, unlike more traditional variables, p53 expression is not an independent predictor of disease outcome in PSCC.     

Tissue polypeptide antigen (TPA) as a prognostic aid in human prostatic carcinoma

Serum levels of tissue polypeptide antigen (TPA) and prostatic acid phosphatase (PAP) in serum, the presence or absence of skeletal metastases, tumor grade, patient age, and erythrocyte sedimentation rate (ESR) were determined in 50 patients with prostatic adenocarcinoma before onset of any therapy. Crude survival rates were estimated for a 5-year period after the time of diagnosis. The prognostic value was estimated by means of the log rank test and multivariate life table analysis. The TPA, PAP, tumor stage, and ESR all appeared to be useful as prognostic markers. Tumor grade and patient age were not significantly related to crude survival. The TPA proved to be the most reliable prognostic marker in single test estimates as well as in a multivariate life table analysis (p less than 0.01).     

Clinical relevance of Fas (APO-1/CD95) expression in laryngeal squamous cell carcinoma.

BACKGROUND: Expression of Fas receptors renders tumor cells potentially susceptible to the host immune system. In squamous cell carcinomas of the head and neck, Fas has recently been found to be down-regulated in some cases; its prognostic value and correlation with clinicopathologic parameters, however, is yet to be delineated. METHODS: Paraffin-embedded specimens of 88 primary laryngeal squamous cell carcinomas were investigated for Fas protein expression by immunohistochemistry. Apoptotic tumor cells were visualized using the nick end labeling method. To assess the immunologic reaction to the neoplasm, the intensity of lymphoplasmocytic stroma reaction was determined. The mean follow-up time amounted to 45.9 months (range, 1-144 months). RESULTS: In tumor-adjacent normal mucosa and in most well-differentiated tumors, Fas expression was restricted to basal and parabasal cell layers. A diffuse pattern of staining reactions predominated in high-grade lesions (p <.001). The degree of Fas expression revealed a positive relationship with the intensity of lymphoplasmocytic stroma reaction (p =.002) but was unrelated to clinicopathologic parameters and to apoptotic rates of tumors. Neither Fas nor the lymphoplasmocytic stroma reaction had any impact on patient survival. CONCLUSIONS: Up-regulation of cell surface Fas expression in laryngeal carcinoma seems to have a stimulatory effect on the immune cell infiltration of the stromal tissue. Its lack of clinical relevance might be due to an inhibition of intracellular Fas signal transduction, which represents a frequent strategy of tumor cells to escape Fas-mediated apoptosis.     

Studies on antigen associated with human squamous cell carcinoma (SCC antigen) in patients with esophageal carcinoma

The authors studied on SCC antigen in patients with esophageal carcinoma. Serum SCC antigen was found in 9 (40.9%) of 22 patients with esophageal squamous cell carcinoma and 5 (55.5%) of 9 patients with lung squamous cell carcinoma, but was not found in other malignant diseases, such as gastric cancer, hepatoma, colon cancer, pancreas cancer and biliary try tract cancer. SCC antigen positive cases increased in association with progression of histological invasion, grade of nodal metastasis and clinical stage. However, in early esophageal carcinoma, SCC antigen was rarely positive. There was no positive case in patients with poorly differentiated squamous cell carcinoma regardless of clinical stage. Positive rate of SCC antigen increased in association with progression of clinical stage in patients with moderately and well differentiated squamous cell carcinoma. Immunoreactivity of SCC, which was investigated immunohistologically with TA-4 rabbit serum, was not found in cases with poorly differentiated squamous cell carcinoma, but was found in keratinized portion and cytoplasm of moderately and well differentiated carcinoma. From the above, SCC antigen is intimately related with keratinization of squamous cell carcinoma, and it was thought that it could be useful as a good marker for diagnosis of moderately and well differentiated squamous carcinoma of the esophagus.     

Tissue concentrations of tissue polypeptide antigen (TPA) and prostatic specific antigen (PSA) in 42 patients with prostatic carcinoma

BACKGROUND: Following development of methods to quantitate biochemical markers in aspiration biopsies we showed that tissue concentration of prostate specific antigen (T-PSA) decreased with increasing malignancy while serum PSA increased. We also found that T-PSA predicts the clinical outcome better than earlier used prognostic markers. METHODS: In order to further study biochemical markers in prostatic cancer a membrane protein, tissue polypeptide antigen (TPA), which is a complex of polypeptide fragments of cytokeratins 8, 18, and 19, was quantitated in 42 patients with newly diagnosed carcinoma of the prostate. The samples had previously been analyzed for T-PSA. RESULTS: Correlation to TGM classification showed that higher malignancy is correlated to lower tissue TPA values. There is a significant positive correlation (r(s) = 0.49, P < 0.01) between T-TPA and T-PSA. Pretreatment values of T-PSA, but not T-TPA, had association to time to progression or time to death. CONCLUSIONS: Increasing prostatic malignancy is correlated to decreasing values of T-TPA. This indicates that the concentrations of membrane and secretory proteins are changed in the same direction in tissue during cancer development. Tissue TPA seem to have no prognostic value in endocrine treatment of prostatic carcinoma.     

Dysadherin expression in head and neck squamous cell carcinoma: association with lymphangiogenesis and prognostic significance

Dysadherin is a recently characterized cancer-associated cell membrane glycoprotein that has a crucial role to cell-cell adhesiveness. The aim of this study was to examine dysadherin expression in head and neck squamous cell carcinoma (HNSCC). A total of 108 tissue specimens of patients with HNSCC were examined using immunostaining for dysadherin, E-cadherin, and the specific lymphatic endothelium marker D2-40. We quantified dysadherin and E-cadherin expression, assessed intratumoral (ILD) and peritumoral lymphatic density (PLD), and examined the possible associations of all the above parameters with clinicopathologic features and outcome. Finally, we used double staining with dysadherin and D2-40 to examine the expression pattern of dysadherin simultaneously with the lymphovasculature environment of HNSCC. High dysadherin expression was correlated with higher clinical stage (chi2, P = 0.01), with the presence of lymph node metastasis at the time of diagnosis (chi2, P = 0.02), and with increased ILD (chi2, P = 0.001). We observed an impressive reverse association between increased dysadherin expression and decreased E-cadherin expression (chi2, P < 0.001). Surprisingly, dysadherin-positive cancer cells usually gathered around areas of high intratumoral lymphatic vessel concentration, surrounding and invading small intratumoral lymphatics. Higher clinical stage and increased dysadherin expression were found to be the only significant independent prognostic factors for overall survival (hazard ratio, 3.94; 95% confidence interval, 1.09-14.27 for clinical stage; hazard ratio, 3.92; 95% confidence interval, 1.46-10.51 for dysadherin). The loss of intercellular adhesiveness and increased dysadherin expression seems to be related to lymphangiogenesis in HNSCC, but this should be confirmed by additional studies. Dysadherin expression might be a promising prognostic marker for separation of patients at higher risk.     

Radiotherapy response in oral squamous carcinoma cell lines: evaluation of apoptotic proteins as prognostic factors

BACKGROUND: In this study, we investigated the importance of apoptosis for cell death after radiotherapy, and whether the expression of pro- and anti-apoptotic proteins has any correlation to the radiosensitivity. METHODS: Three oral squamous cell carcinoma cell lines, UT-SCC-2, UT-SCC-9 and UT-SCC-24A, were subjected to radiotherapy. After irradiation, viable and dead cells were counted to determine radiation sensitivity and apoptosis was analyzed by measurement of caspase-3 activity. The expressions of pro- and anti-apoptotic proteins were assessed using western blot analyses. RESULTS AND CONCLUSION: After irradiation, apoptotic morphology and caspase-3 activity were only detected in cell lines exhibiting high or moderate radiosensitivity. Western blot analysis indicates that survivin, epidermal growth factor receptor, cyclooxygenase-2, and Bcl-x(L) are critical components in irradiation resistance of the investigated cell lines. Moreover, our results suggest that apoptotic cell death and the balance between pro- and anti-apoptotic proteins are of importance for the outcome of radiotherapy.     

Urokinase-type plasminogen activator (uPA) and its inhibitor--new prognostic factors in oral squamous cell carcinoma

Several cell biological studies have shown that the invasiveness of different malignant tumors (breast, renal, prostate, gastric, ovarian cancers) depends at least in part on the urokinase type plasminogen activator (uPA) and its inhibitor PAI1. uPA converts plasminogen into plasmin. Plasmin degrades tumor matrix components and starts invasion and metastasis. Our target was to see the possible prognostic relevance of the tumor-associated proteolytic factors and to compare with tumor size, nodal status and grading. Our results suggest that the invasive and metastatic potential of squamous cell carcinoma is correlated with overexpression of uPA and PAI1.     

CRYAB在肺鳞癌中的表达及其临床意义

目的 检测分析CRYAB表达与肺鳞(LUSC)癌重要临床指标之间的关系。方法 选取2014年01月～2016年12月间LUSC病人癌组织及癌旁组织20例,采用qPCR检测CRYAB在肺鳞癌病人中的表达情况,在59例LUSC组织芯片上进行免疫组化检测,使用Cox回归分析法及Kaplan-Meier生存分析法进行肺鳞癌病人的预后评估。结果 LUSC中CRYAB mRNA表达值为4.456±1.512,癌旁组织为2.944±0.4907,两组比较差异有统计学意义(P<0.05);LUSC中的CRYAB蛋白表达高于癌旁组织,两组比较差异有统计学意义(P<0.05)。CRYAB的表达与LUSC的T分期显著相关(P<0.05)。单因素及多因素生存分析显示,CRYAB表达与LUSC预后关系密切(P<0.05),CRYAB高表达提示预后不良。结论 CRYAB在肺鳞癌病人显著高表达,CRYAB的表达与肺鳞癌的恶性表型相关。CRYAB可作为肺鳞癌病人预后的独立危险因素。