Prognostic value of epidermal growth factor receptor expression in cervical carcinoma.

AIMS: To investigate the pattern of epidermal growth factor receptor expression and its prognostic value in the three main types of cervical carcinoma. METHODS: 62 cases of stage IB/IIA cervical carcinoma, all with a minimum of five years of follow up, were studied. Representative sections were stained for mucin to permit accurate tumour typing and a standard avidin-biotin immunoperoxidase technique using the polyclonal antibody 12E was used to demonstrate the presence of epidermal growth factor receptor. RESULTS: A proportion of all three tumour types expressed epidermal growth factor receptor, it being most common in squamous cell carcinomas (50%). Overall, there was a correlation between epidermal growth factor expression and mortality. This was particularly obvious in the absence of lymph node metastases. When the individual tumour types were considered this association with prognosis was not demonstrable for squamous cell carcinomas or adenocarcinomas but was a very prominent feature of adenosquamous carcinomas. CONCLUSIONS: Immunohistochemical demonstration of epidermal growth factor receptor expression may be useful in identifying those patients with a poor prognosis, particularly those with adenosquamous carcinomas which have not metastasised to the regional lymph nodes.     

Prognostic value of bcl-2 expression in patients with operable carcinoma of the uterine cervix.

AIM: To evaluate the patterns of bcl-2 expression in early stage cervical carcinoma; to compare bcl-2 expression with clinicopathological findings; and to assess its prognostic value. METHODS: Wertheim radical hysterectomy specimens from 76 patients (FIGO stages Ia-IIb) with untreated nonmetastatic invasive cervical carcinoma were studied. Expression of bcl-2 was detected immunohistochemically using a monoclonal antibody. A tumour was regarded as positive when more than 5% of the neoplastic cells exhibited bcl-2 immunoreactivity. RESULTS: Forty eight (63%) cervical carcinomas were scored as bcl-2 positive and 28 (37%) as bcl-2 negative. Most tumours showed heterogeneous cytoplasmic staining. Bc1-2 immunoreactivity did not correlate with tumour histology, tumour stage, presence of lymph node metastases, or involvement of the lymphovascular space. The five year survival rate for patients with bc1-2 negative tumours was 34% and was 71% for patients with bc1-2 positive tumours. On multiple regression analysis (Cox proportional hazards model), bc1-2 expression and vascular permeation were independent predictors of overall survival. CONCLUSIONS: Bcl-2 expression seems to be associated with less aggressive behaviour in early stage cervical carcinoma. The transition to bcl-2 independence may play an important role in tumour progression.     

Prognostic value of p53, bcl-2, and c-erbB-2 protein expression in phaeochromocytomas

Many studies have tried to discriminate malignant from benign phaeochromocytomas, but until now no widely accepted histological, immunohistochemical, or molecular methods have been available. In this study of 29 malignant and 85 benign phaeochromocytomas from 102 patients, immunohistochemistry was performed with antibodies to the tumour suppressor gene product p53 and the proto-oncogene products bcl-2 and c-erbB-2, using the avidin–biotin complex method. Malignant phaeochromocytomas showed a statistically significant higher frequency of p53 (p=0·042) and bcl-2 (p=0·037) protein expression than their benign counterparts. The combination of both markers showed an even higher significance (p=0·004), to which both markers contributed equally. Overexpression of c-erbB-2 was associated with the occurrence of familial phaeochromocytomas (p=0·001), but no difference was found between benign and malignant cases. In conclusion, p53, bcl-2, and c-erbB-2 all appear to be involved in the pathogenesis of a proportion of phaeochromocytomas. Immunoreactivity to p53 and bcl-2 proteins may help to predict the clinical behaviour of phaeochromocytomas. Copyright © 1999 John Wiley & Sons, Ltd.     

Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

OBJECTIVE:

To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer.

MATERIALS AND METHODS:

A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2‐40.

RESULTS:

Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6%) cases, with 29/31 (93.5%) of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node‐positive cases was lower than that of node‐negative (18.9% vs. 22.6%, respectively). Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8%) cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively), although this difference was not significant.

CONCLUSIONS:

These preliminary results suggest that podoplanin may have a role in host‐tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas.     

Lack of c-erbB-2 oncoprotein expression in male breast carcinoma.

A series of 21 male breast carcinomas were immunostained using NCL-CB11, an antibody directed against the internal domain of the c-erbB-2 transmembrane oncoprotein. In contrast to female breast cancer, where up to 35% of cases show positivity, all of these cases were negative. This suggests that no prognostic information regarding patient survival can be made in these patients and that male breast carcinomas may be under different growth control mechanisms from female breast carcinomas.     

c-erbB-2 oncogene product expression and prognosis in gastric carcinoma.

The prognostic value of c-erbB-2 protein expression was assessed retrospectively in 87 "curative" gastrectomy specimens from patients with gastric carcinoma. Tumours were stained immunohistochemically with the specific antibody 21N. Eight (9%) cases had strong membrane staining, all of which were of the intestinal type, and lymph node metastases, which showed concordance of staining in seven cases. In contrast to studies in breast cancer, positive cases showed a trend towards better five year survival, but this did not reach significance.     

c-erbB-2 expression in different histological types of invasive breast carcinoma.

Sections of 149 breast carcinomas were examined for the over-expression of c-erbB-2 oncoprotein using the avidin-biotin immunoperoxidase technique and two different specific antibodies. These included the polyclonal antibody 21N and the monoclonal antibody 4D5. The tumours were divided into two main groups. The first included 75 cases of invasive ductal and classic invasive lobular carcinomas. The second group consisted of 74 cases with histological types known to have a good prognosis, including mucinous, alveolar variant of invasive lobular, medullary, tubular, cribriform and papillary carcinomas. Fifteen (20%) tumours of the first group were positive with the two antibodies. Fourteen of these were of the ductal type and one was a mixed invasive ductal and lobular carcinoma. Ten of the pure ductal cases had areas of comedo carcinoma. The intraductal elements in a further tumour were positively stained with 21N antibody only. None of the second group of tumours, which included histological types known to have good prognosis, stained with 4D5, although one mucinous carcinoma was positively stained with 21N. These findings suggest that in invasive breast carcinoma immunostaining for c-erbB-2 is mainly seen in a subgroup of ductal tumours, and that almost all other histological types, especially those associated with good prognosis, lack this expression.     

Cyclooxygenase-2 and c-erbB-2 expression in colorectal carcinoma assessed using tissue microarrays.

The c-erbB-2 and cyclooxygenase (COX) pathways are involved in the pathogenesis of colorectal carcinoma, but the relationship is not fully understood. This study evaluated the significance of c-erbB-2, COX-2, and Ki-67 protein expression in 185 patients with colorectal carcinoma using tissue microarrays. Only one case expressed cerbB-2 protein. COX-2 expression was noted in 166 of 176 cases (94.3%), and the Ki-67 expression rate averaged 5.9%. There was no relationship among c-erbB-2, COX-2, and Ki-67 protein expression, and COX-2 protein expression was not related to tumor stage, differentiation, size, depth of invasion, lymphatic or vascular invasion, or patient survival. While the contribution of c-erbB-2 to colorectal carcinogenesis may be of little quantity, COX-2 may be deeply involved in colorectal carcinogenesis.     

食管癌细胞中c-erbB-2与P-gP表达的相关性

目的　探讨食管癌细胞c erbB 2与多药耐药性相关性及其临床意义。方法　用免疫组化方法检测癌细胞c erbB 2和用流式细胞术检测了 4 6例食管癌手术标本中癌细胞P 糖蛋白 (P gp)表达水平 ,并进行相关性分析。 结果　食管癌中c erbB 2表达阳性 12 / 4 6例 (2 6 1% ) ;P gp表达阳性 2 8/ 4 6例 (6 0 9% )。食管癌淋巴结转移情况与c erbB 2和P gp表达比较发现 ,在c erbB 2阳性时淋巴结有转移 (31 0 9%± 5 33% )与无转移 (8 0 4 %± 3 0 3% )组的P gp表达比较差异有显著性(P =0 0 0 73) ,而在c erbB 2阴性时淋巴结转移情况与P gp表达无相关性。食管癌临床分期与c erbB 2和P gp表达比较发现 ,在c erbB 2阳性时 ,Ⅲ～Ⅳ期 (33 6 8%± 5 5 1% )与Ⅱ期 (9 30 %± 2 78% )组P gp表达比较 ,差异有显著性 (P =0 0 0 2 7) ,而在c erbB 2阴性时临床分期与P gp表达无相关性。食管癌肿瘤大小、肿瘤分化程度与c erbB 2和P gp表达均无相关性。结论　在c erbB 2表达阳性时食管癌中有淋巴结转移、临床Ⅲ～Ⅳ期患者与P gp表达升高有相关性 ,提示双阳性时肿瘤患者预后较差。但在c erbB 2表达阴性时食管癌有淋巴结转移、临床分期与P gp表达无相关性     

基质金属蛋白酶在宫颈肿瘤中的表达及其意义

流行病学研究和实验室研究已经充分证明了,人乳头瘤病毒（HPV）的持续感染在宫颈肿瘤的形成过程中起到重要作用。而肿瘤进展的基本过程是肿瘤细胞的浸润和转移。目前许多关于此方面的研究都将焦点集中于基质金属蛋白酶（MMPs）对细胞外基质的降解上。并且研究显示MMPs（尤其是MMP-2,MMP-9）表达的上调与肿瘤的浸润、转移密切相关。本文对MMP-2、MMP-9在宫颈癌前病变组织和癌组织中的表达和活性进行综述,以寻求对宫颈肿瘤新的诊断和治疗手段。     

Prognostic value of prostaglandin F2 alpha concentrations in breast carcinoma.

Prostaglandin F2 alpha (PGF2 alpha) concentrations were measured by radioimmunoassay in homogenised primary tumours from 57 patients with breast cancer. These patients were followed up from 60 to 78 months (median 63 months) after surgery and PGF2 alpha concentrations were related prospectively to metastatic spread and survival. The amounts of PGF2 alpha varied greatly in the different tumours (range 0-90 ng/mg protein), but no significant association was found between PGF2 alpha concentrations and disease free survival, time of relapse, site of recurrence, or overall survival. It therefore seems unlikely that measurement of PGF2 alpha in breast carcinoma is important in the prognosis of the disease.     

Prognostic value of TROP2 in human nasopharyngeal carcinoma

Background: There is increasing evidence demonstrating the role of human trophoblast cell surface antigen 2 (TROP2) in cancer development and progression. However, their prognostic value in Epstein-Barr virus (EBV) associated nasopharyngeal carcinoma (NPC) remains to be elucidated. Method: The prognostic significances of TROP2 and Ki-67 were determined by immunohistochemistry in 58 NPC samples. TROP2 mRNA expression level and biological functions were evaluated. The presence of EBV was assessed using in situ hybridization. Analyses were conducted on the association between each of these variables as well as clinical outcome. Results: TROP2 was exhibited over expression in 64% of NPC samples and significantly associated with highly proliferative tumor cells (P = 0.05) and lymph node metastases (P = 0.03). Overexpression of TROP2 significantly correlated with worse overall survival (P = 0.026) and poor disease-free survival (P = 0.021). By univariate analysis, high expression of TROP2 significantly correlated with patients with distant metastases, Ki-67 and EBV infection. Multivariate analysis further revealed that TROP2 along with Ki-67 and distant metastasis are independent prognostic predictors for NPC patients. Conclusion: Our findings have demonstrated that overexpression of TROP2 appears to be an independent predictor for poor clinical outcome in NPC. The strong correlation of overexpression of TROP2 with Ki-67 and distant metastases indicates a potentially therapeutic strategies targeting TROP2 for NPC patients.     

Prognostic value of activated Akt expression in oral squamous cell carcinoma

BACKGROUND: Akt is a serine/threonine kinase that plays an important role in tumorigenesis and influences prognosis in several cancers. However, its importance in oral squamous cell carcinomas (OSCC) has not been elucidated. AIM: To investigate the association between the expression of activated Akt, clinicopathological factors, and E-cadherin, PCNA (proliferating cell nuclear antigen), and VEGF (vascular endothelial growth factor) expression to verify the validity of Akt as a prognostic factor in OSCC. METHODS: Phosphorylated Akt (p-Akt), E-cadherin, PCNA, and VEGF expression were assessed immunohistochemically in 84 OSCCs. The results were analysed in relation to clinicopathological factors. RESULTS: p-Akt was expressed in 29 cases. It was significantly correlated with lymph node metastasis, TNM stage, and E-cadherin expression. Univariate analysis showed that p-Akt expression, E-cadherin expression, PCNA expression, differentiation, tumour size, lymph node metastasis, TNM stage, and recurrence correlated with prognosis. Multivariate analysis showed that p-Akt expression is an independent prognostic factor in patients with OSCC. CONCLUSIONS: This study revealed that Akt activation is a significant prognostic indicator for OSCC and is correlated with E-cadherin expression. The inhibition of Akt is a possible molecular approach to the treatment of OSCC.     

Correlation between EGFR and c-erbB-2 oncoprotein status and response to neoadjuvant chemotherapy in cervical carcinoma.

Neoadjuvant chemotherapy prior to definitive radical surgery or radiotherapy may be effective in reducing tumor volume or clinical stage and may even enhance pelvic control and survival. However, there are significant limitations to the use of neoadjuvant therapy in the non-responder group. They include delayed total treatment course, the presence of drug resistant clones which result in accelerated tumor growth, and limited bone marrow reserve for subsequent definitive therapy. Thus, there is a need to identify parameters providing a more precise indication of the response to neoadjuvant chemotherapy in patients with invasive cervical cancer. From Jan. 1995 to Jan. 1996, neoadjuvant chemotherapy with 3 courses of cisplatin and vincristine was used in 32 patients with invasive cervical cancer (FIGO stage Ib to IIIb; tumor size greater than 2 cm). Prior to chemotherapy, quantitative tissue levels of epidermal growth factor receptor (EGFR) and c-erbB-2 oncogene protein were measured by using an enzyme-linked immunosorbent assay (ELISA). Tumor size was estimated before and after chemotherapy. Relations between oncoproteins and reductions of tumor size were evaluated. Tumor size prior to neoadjuvant chemotherapy did not show any correlation with either the concentrations of EGFR or c-erbB-2 oncoprotein. As well, the tumor reduction index did not manifest any correlation with EGFR, it did had an inverse linear correlation with the c-erbB-2 oncoprotein levels (Rs = -0.71, P < 0.05). The results of this study suggest that c-erbB-2 oncoprotein is associated with a reduced response to neoadjuvant chemotherapy in primary treatment of invasive cervical cancer and may be useful in directing therapeutic approaches.     

Prognostic value of vascular endothelial growth factor expression in primary lung carcinoma

To investigate whether an association exists between vascular endothelial growth factor (VEGF) expression and tumor prognosis in primary lung carcinoma, we used immunohistochemical techniques to analyze microvessel density and VEGF expression in lung carcinoma tissue from 98 patients. Tissue had been fresh-frozen at the time of operation and preserved for more than 5 years. The results indicated that VEGF expression was positive for 50 of the 98 patients (51.0%), with 27 (27.6%) being weakly positive and 23 (23.5%) being strongly positive. The microvessel density in tissue showing weakly positive and strongly positive VEGF expression was significantly higher than that in VEGF-negative tumor tissue (P < 0.05: negative vs. weakly positive, P < 0.01: negative vs. strongly positive), we showed demonstrating that VEGF expression was significantly associated with intratumoral microvessel density. The 5-year survival rates were 8.7% for strongly VEGF-positive patients, 43.9% for weakly VEGF-positive patients and 79.2% for VEGF-negative patients, respectively (P < 0.01: negative vs. weakly positive or strongly positive). Furthermore, multivariate analysis employing multiple regression analysis indicated that VEGF expression correlates highly with the overall survival rates of patients with primary lung carcinoma. Two variables, N status and VEGF expression, were found to be significant prognostic factors (P < 0.01). The results of this study suggest that VEGF expression is associated with intratumoral microvessel density. VEGF expression may constitute important independent prognostic evidence that can help us in predicting the outcomes of patients with primary lung carcinomas.     

c-myc, c-erbB-1 and c-erbB-2 expressions in urothelial carcinoma

The expression of c -myc , c- erb B-1 and c- erb B-2 In 24 cases of urothelial carcinoma by Southern and northern blot analysis, and immunohistochemistry was examined. The results were compared with the pathological grade and stage. We found elevated mRNA expressions of c- myc and c- erb B-1 In 19 and 11 of 21 cases, respectively, but there was no apparent amplification or rearrangement of these oncogenes in any of the cases examined. By immunohistochemistry using anti-epidermal growth factor receptor antibody, most of the cases showed positbe immunoreactivity on the cancer cell membranes, and cancers of higher pathological grade and stage showed more intense staining. By contrast, amplification of c- erb B-2 was detected in four of 24 cases, all of which were assigned to a high pathological grade (G3). Elevated c- erb B-2 mRNA levels appeared to correlate with the pathological grade of the cancers. Positive immunohistochemical reactions to c- erb B-2 were found in the cancer cell membranes in three of 24 cases, which were accompanied by amplification and eievated mRNA levels of c -erb B -2 . In conclusion, expressions of c- myc , c- erb B-1 and c- erb B-2 were all elevated in the majority of urothellal carcinomas, but the amplification was not universal.     

Sebaceous carcinoma of the eyelids: frequent expression of c-erbB-2 oncoprotein

Ocular sebaceous carcinoma (OSC) is an uncommon malignancy with a potential to recur and metastasize. Some characteristics of sebaceous carcinoma, such as female preponderance, shown in the present series during 11-year period at Korea Cancer Center Hospital, led us to study their hormone receptors and c-erbB-2 expression. c-erbB-2 overexpression was very common (83%) in OSC, and was not associated with pathologic findings or clinical outcome. Interestingly, estrogen and progesterone receptor was detected in 4 and 2 cases, respectively, suggesting a role of hormonal influence on this neoplasm. Immunohistochemical and clinicopathologic features of 18 cases of OSC in Korea are presented.