Oestrogen receptor and epidermal growth factor receptor expression in male breast carcinoma.

Male breast carcinomas are probably hormone-dependent, but receptor studies are few because this is a relatively rare tumour. We have studied 21 cases of male breast carcinoma immunohistochemically for oestrogen receptor (ER) and epidermal growth factor receptor (EGFR) expression employing the antibodies ER-ICA and 12E on formalin-fixed, paraffin-embedded material. In our series, 86 per cent of male breast cancers were ER-positive and 76 per cent were EGFR-positive. Male breast carcinomas do not exhibit the inverse correlation between ER and EGFR expression that characterizes female breast carcinomas. Owing to the limitations of a small series, we were unable to comment on the relationship between ER and EGFR expression and patient survival. However, the relatively high incidence of ER expression may provide a growth advantage for this tumour in a male environment characterized by low levels of oestrogen. In addition, high EGFR expression may also contribute to a poor prognosis independent of ER status.     

Immunohistochemical investigation of epidermal growth factor receptor expression in ameloblastomas

Immunohistochemical analysis was performed to determine the localization of epidermal growth factor receptor (EGFR) in ameloblastomas. Ameloblastoma samples were classified into follicular, plexiform, and basal cell types. The number of cases in each category was 17, 19 and 3, respectively. Ameloblastomas, disregarding their histological type, consist of two cell forms: peripheral columnar cells and central stellate cells. The frequency of EGFR expression was much higher in the latter than in the former (P<0.005). On analysis with respect to histological types, the frequency of EGFR expression in columnar cells was not significantly different between the follicular and the plexiform types, but was observed more frequently in the stellate cells in the follicular than in the plexiform ameloblastomas (P<0.05). This pattern of EGFR expression was not consistent with the PCNA staining pattern, but was similar to that of keratin expression which we have reported previously. The present study suggests that EGFR expression in ameloblastomas is closely associated with tumour differentiation, and squamous differentiation in particular.     

表皮生长因子受体在口腔鳞癌组织中的表达及意义

目的：研究表皮生长因子受体（ＥＧＦＲ）在口腔鳞癌组织中的表达及其临床病理学意义。方法：采用免疫组化Ｓ－Ｐ法对６５例不同分化的口腔鳞癌组织及１０例正常口腔粘膜组织进行ＥＧＦＲ检测。结果：ＥＧＦＲ在鳞癌组织中呈异质性表达,其阳性率（６１．５％）明显高于正常口腔粘膜组织（Ｐ〈０．０１）;ＥＧＦＲ表达状况与鳞癌组织学分级,区域淋巴结转移及患者预后间存在相关关系（Ｐ〈０．０１或０．０５）。结论：ＥＧＦＲ在口     

The behaviour of human oral squamous cell carcinoma in cell culture.

This study examined the initial behaviour of 48 human oral squamous cell carcinomas (SCC) in cell culture. The early outcome of these cultures (contamination, absence of cell growth, epithelial cell senescence/fibroblast overgrowth, extended keratinocyte growth) did not reflect the clinical characteristics of the tumours of origin. Four new human oral SCC cell lines were characterized more extensively. Each cell line was immortal, 3T3-independent, and expressed low degrees of anchorage independence (CFE less than 4 per cent). Two of the four cell lines were tumorigenic in athymic mice. All of the cell lines expressed keratin intermediate filaments and two showed weak co-expression of vimentin. A wide range of keratins were expressed by the tumour xenografts; cornified keratins (K1, K10) were only expressed in the absence of K19 and vimentin, and vice versa. The nuclear:cytoplasmic ratio and the degree of serum independence correlated with each other and with the STNMP clinical grading of the tumours of origin.     

表皮生长因子受体和P53与食管鳞状细胞癌放疗敏感性的关系

目的 分析食管鳞状细胞癌患者标本中表皮生长因子受体(EGFR)和P53表达水平与其临床病理特征的相关性,探讨术前放疗对EGFR和P53表达的影响,为临床食管鳞状细胞癌手术联合放疗的治疗策略提供理论依据.方法 采用免疫组织化学方法检测食管鳞状细胞癌患者标本中EGFR、P53蛋白的表达水平,分析其表达与食管鳞状细胞癌临床病理参数的关系,对比术前放疗对患者癌组织中EGFR和P53表达水平的影响.结果 与正常食管黏膜上皮组织相比,食管鳞状细胞癌组织中EGFR和P53的表达水平均显著升高;食管鳞状细胞癌组织中EGFR和P53的表达均与其组织学分级、浸润程度、有无区域淋巴结转移呈正相关;术前放射治疗可显著降低食管鳞状细胞癌组织中EGFR和P53的表达水平.结论 在食管鳞状细胞癌中,EGFR和P53的表达水平与其临床病理特征有密切关系,且呈正相关,检测两种蛋白的表达水平对食管鳞状细胞癌的恶性程度及预后判断具有重要的临床意义.     

新疆地区口腔鳞状细胞癌中PLCE1蛋白的表达及临床意义

目的探讨PLCE1蛋白在新疆地区口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的表达及预后价值。方法采用免疫组化EnVision两步法检测124例OSCC及63例癌旁正常组织中PLCE1蛋白的表达,分析其表达与OSCC临床病理特征及预后的关系。结果OSCC及癌旁组织中PLCE1蛋白高表达率分别为41.9%(52/124)和0(0/63),差异有统计学意义(P<0.0001)。PLCE1诊断OSCC的ROC曲线下面积(AUC)为0.954(敏感度83.9%,特异性95.2%)。Kaplan-Meier及Cox单因素分析显示,PLCE1高表达(P=0.004、P=0.006)和T分期(P=0.002、P=0.004)是影响患者不良预后的危险因素。Cox多因素分析结果显示,PLCE1高表达(P=0.008)和T分期(P=0.005)是患者预后的独立因素。结论PLCE1蛋白在新疆地区OSCC组织中高表达,且与患者不良预后相关,可作为肿瘤患者不良预后的新型生物标志物。     

Primary adenoid squamous cell carcinoma of the oral cavity

Adenoid squamous cell carcinoma (ASCC) is an uncommon but well-recognized variant of squamous cell carcinoma that was first described by Lever in 1947. ASCC has been reported to originate in the sun-exposed skin of the head and neck and in other sites. An additional case of ASCC is reported here. The patient was a 64-year-old Japanese woman who requested examination of a reddish lesion on the left floor of the mouth. The biopsy material was diagnosed as squamous cell carcinoma. Clinical examination showed a well-circumscribed, 20 x 10 mm-sized lesion, which was categorized as cT2cN0cm 0. Tumor resection was therefore performed. Histologically, most parts of the lesion were conventional squamous cell carcinoma in situ, but the invasive part consisted of ASCC with gland-like or reticular appearance. The latter part was negative for mucin staining. Immunohistochemically, this lesion was positive for pancytokeratin, high-molecular-weight keratin, cytokeratin (CK) 7/8, CK19, E-cadherin and p53, but negative for vimentin, CK20, and S-100 protein. The Ki-67 labeling index was 50.3% in the ASCC part and 34.5% in the carcinoma in situ part. These findings and a review of the literature indicate that a gland-like feature of ASCC is associated with the loss of cell adhesion in the center of the cancer nests, and it can be confirmed simply by mucin staining to be neither an adenosquamous carcinoma nor ductal involvement of conventional squamous cell carcinoma.     

Epidermal growth factor receptor (EGFR) and squamous cell carcinoma of the skin: molecular bases for EGFR-targeted therapy

Cutaneous squamous cell carcinoma (SCC) ranks second in the frequency of all skin tumors. Its incidence has risen significantly due to an increased sun exposure and the number of immunocompromised patients. It has a well-defined progression with known precursor lesions called actinic keratosis. The degree of cellular differentiation, tumor thickness, location, and other features has prognostic value. It has a better prognosis than mucosal SCC of the head and neck, also called head and neck squamous cell carcinoma (HNSCC).Ultraviolet light plays a fundamental role as an initiator and promoter of carcinogenesis of SCC, allowing the accumulation of genetic alterations that allows a selective growth advantage. The TP53 (p53) gene often mutates and Ras is frequently activated, but with low frequency of mutations. Normally, the extracellular signals determine whether the cells move from a quiescent state into an active proliferative state. In tumor cells an increase in the production of growth factors and its receptors can be often seen that gives rise to such an autocrine circuit facilitating cellular division. Recently, frequent mutations in the epidermal growth factor receptor (EGFR) have been detected in lung cancer, mainly deletions in exon 19 and L858R mutation in exon 21. These are located at the EGFR tyrosine kinase domain (TK). EGFR TK mutations produce activation of the signaling pathways downstream and preferentially activated antiapoptotic pathways (PI3K/AKT, JAK-STAT and ERK/MAPK). These mutations are correlated with the clinical response of patients to tyrosine kinase inhibitors (gefinitib and erlotinib), because the tumor cells are addicted to the constant activation of specific signaling pathways. Glioblastoma shows another EGFR mutation (EGFRvIII), corresponding to a deletion of the extracellular domain, and it is present in 24-67% of these tumors. This variant has been found in 42% of HNSCC, related to the poor response to monoclonal antibody cetuximab.Many observations show that there are abnormalities in the expression of epidermal growth factor receptor (EGFR) and/or its ligands in HNSCC with frequent activation of multiple pathways downstream EGFR, and unrelated to RAS mutation. This suggests the possibility of activation by mutation or overexpression of a component of the pathway located upstream-Ras. While in other tumors, especially lung cancer and glioblastoma, the EGFR mutations are frequent genetic events, it is unknown whether EGFR is mutated or amplified in SCC of the skin and what would be its pathogenic role in this malignancy and its precursors.     

鼻咽癌中表皮生长因子受体与相关信号蛋白关系及对细胞增殖的影响

目的 研究表皮生长因子受体(EGFR)与细胞增殖相关信号分子p-ERK、c-fos、Ki-67在鼻明癌及鼻咽黏膜上皮中表达的关系及其抑制剂西妥昔(Cetuximab)对鼻咽癌CNE-2Z细胞增殖的影响.方法 用链霉菌抗生物索蛋白-过氧化物酶(SP)法检测30例鼻咽癌(男性22例,女性8例;年龄28～70岁,中位年龄49...     

Disappearance of epidermal growth factor receptor is essential in the fusion of the nasal epithelium

Epidermal growth factor (EGF) and receptor (-R) signaling pathway is required for epithelial cell growth and differentiation such as the degeneration of the medial edge epithelial cells during the fusion process of secondary palate formation. As epithelial fusion takes place during primary palate formation, we investigated the involvement of the EGF-R in fusion of the medial (MNP) and lateral (LNP) nasal prominences of the mouse embryo was examined. Immunoreactivity of EGF-R was investigated in embryonic day 10 embryos (32–37 somite stages). The EGF-R immunoreactivity was observed in the nasal epithelia of the presumptive fusion area before fusion. It became undetectable just prior to the fusion and faintly reappeared at the time of the fusion. In contrast, the non-fusing epithelial cells of the nasal groove maintained the immunoreactivity throughout these stages. In order to elucidate whether the EGF/EGF-R signaling pathway was involved in nasal epithelial fusion, EGF solution was injected into the exocoelum of explanted mouse embryos, and the embryos were cultured for 18–24 h by whole embryo culture (WEC). This exogenous EGF inhibited fusion of nasal pro-minences in 66.7–81.5% of the embryos. Treatment with EGF for 4–14 h showed that exogenous EGF dis-turbed the EGF-R disappearance and normal alteration of epithelial cell morphology in the fusion area. These results suggest that temporal disappearance of the EGF/EGF-R signaling from presumptive fusion of the nasal prominences is required for morphological change of the epithelial cells leading to the fusion of MNP and LNP.     

Clinicopathology significance of podoplanin immunoreactivity in esophageal squamous cell carcinoma

Backgroud and aim: Podoplanin (D2-40) is a specific marker for lymphatic endothelium. The vast majority of previous studies on podoplanin immunostaining in esophageal squamous cell carcinoma (ESCC) focused on identifying lymphatic vessel invasion (LVI) and counting lymphatic vessel density (LVD) and had contradictory results. Recent studies show podoplanin expression on cancer cells or tumor stroma in several cancers, which have specific significance; but the status in ESCC remains unclear. Therefore, the aim of this study was to further study and summarize the clinicopathological significance of podoplanin immunoreactivity in ESCC. Materials and methods: We examined podoplanin expression in tissue specimens from 107 patients with ESCC by immunohistochemistry. Podoplanin positive lymphatic vessels in intratumoral and peritumoral tissues and podoplanin positive expression in cancer cells and tumor stroma were analyzed, and correlated with clinicopathologic parameters and three-year overall and free-disease survival. Results: 34 (31.8%) and 28 (26.2%) of 107 specimens had podoplanin positive expression in cancer cells and tumor stroma, respectively. Logistic regression analysis showed high intratumoral lymphatic vessel density (I-LVD) and podoplanin positivity in cancer cells were increased risks of lymph node metastasis (LNM) (OR = 2.45, P = 0.03; OR = 0.35, P = 0.01, respectively). Survival analysis showed that I-LVD was a significant factor related to poor three-year overall and free-disease survival (P = 0.04, P = 0.03, respectively). Conclusions: Previous data and our results show that podoplanin seems to be a useful marker to predict LNM, recurrence, and worse prognosis in ESCC; in particular, LVI, high I-LVD, and podoplanin positivity in cancer cells are associated with LNM, recurrence and overall survival.     

Basaloid-squamous cell carcinoma of the oral mucosa: Report of two cases and study of the proliferative activity

Two cases of basalold-squamous cell carcinoma (BSC) of the oral mucosa are described. The first case occurred at the floor of the mouth in a 58-year-old man, and the second case occurred at the mandibular gingiva in a 79-year-old woman. The laboratory data of the first case showed a positive response to hepatitis C virus antibody. in the first case, the tumor mass measured 4 times 4 cm in size, and was i-texl at the lingual side of the median mandible beside the sublingual gland. In the second case, the tumor mass measured 25 times 15 mm In size, and was located in the alveolar mucosa of the right mandible. Histologically, both tumors showed a neoplastic epithelium arranged in a solid pattern with evidence of peripheral palisading, central necrosis, and some squamous differentiation. The pro-ilferathfe activities of the BSC were compared with conventional squamous cell carcinomas (SCC) in the oral floor and gingiva, respectively, by employing a sensitive argy-rophillc nuclear organizer region (AgNOR) staining method. The number of AgNOR per nucleus of the BSC was higher than that of any other SCC cases. The results support the opinion that BSC of the oral mucosa has a worse prognosis than conventional SCC.     

Epidermal growth factor receptor: a novel biomarker for aggressive head and neck cutaneous squamous cell carcinoma

There is currently no prognostic tool that reliably predicts the risk of metastasis in cutaneous squamous cell carcinoma, most of which occur in the head and neck region. Epidermal growth factor receptor has received much interest in recent years with the advent of epidermal growth factor receptor-targeted molecular therapy in clinical oncology. We investigate the role of epidermal growth factor receptor as a biomarker for head and neck cutaneous squamous cell carcinoma. Using immunohistochemistry and fluorescence in situ hybridization, we assessed the epidermal growth factor receptor protein expression and gene copy in 3 groups of head and neck cutaneous squamous cell carcinoma: primary lesions not associated with metastasis (P), primary lesions associated with subsequent metastasis (PM), and metastatic nodal disease (M). Epidermal growth factor receptor overexpression was detected in 36% and 79% of P and PM cases, respectively. Epidermal growth factor receptor overexpression was significantly associated with PM (P = .03) and was found to be an independent prognostic factor for metastasis on multivariate analysis (P = .05). However, epidermal growth factor receptor overexpression was only maintained in 47% of cases in the M group. None of the 27 cases that overexpressed the epidermal growth factor receptor protein showed gene amplification: the results were uninterpretable in 2, and polysomy and balanced disomy were detected in 5 and 20 cases, respectively. These observations may have important prognostic and therapeutic implications for head and neck cutaneous squamous cell carcinoma.     

Immunoreactive transforming growth factor alpha and epidermal growth factor in oral squamous cell carcinomas

Forty oral squamous cell carcinomas have been investigated immunohistochemically for the presence of transforming growth factor alpha (TGF-α) and epidermal growth factor (EGF). The same cases were recently characterized for the expression of EGF-receptors. TGF-α was detected with a monoclonal mouse antibody and EGF with polyclonal rabbit antiserum. Thirty-five of the tumours were positive for TGF-α and 26 of the tumours for EGF. None of the poorly differentiated tumours was positive for EGF, but they all were for TGF-α. In sections including normal differentiated oral mucosa, the cells above the basal cell layer were positive for both TGF-α and EGF. The same staining pattern was observed in oral mucosa obtained from healthy persons. In moderately to well differentiated carcinomas, the immunoreactivity was mainly confined to the cytologically more differentiated cells, thus paralleling the situation observed in the normal differentiated oral mucosa. In four cases, material was available from both a primary tumour and a metastasis. Three of these were positive for TGF-α and EGF with the same staining pattern as that of the primary tumours. This investigation together with our previous results confirms the existence of TGF-α, EGF, and EGF-receptors in the majority of oral squamous cell carcinomas and their metastases.     

结直肠癌c—erbB—2,EGFR表达与肿瘤生物学行为的关系

目的：探讨结直肠癌ｃ－ｅｒｂＢ－２及表皮生长因子受体（ＥＧＦＲ）共同表达对其生物学行为及预后的影响。方法：应用免疫组织化学方法检测６９例结直肠癌中ｃ－ｅｒｂＢ－２及ＥＧＦＲ的表达情况。结果：ｃ－ｅｒｂＢ－２和ＥＧＦＲ共同表达时，肿癌细胞增殖指数高，呈浸润性生长方式的较多，病人５年生存率较低。结论：ｃ－ｅｒｂＢ－２和ＥＧＦＲ可能有协同作用，同时检验两者的表达情况可能为临床判断病人预后提供较可靠的依据     

Prognostic value of EGFR family expression in lymph node-negative esophageal squamous cell carcinoma patients

The human epidermal growth factor receptor (EGFR) family has been widely studied in cancer, however, the prognostic role of EGFR family expression in lymph node-negative esophageal squamous cell carcinoma (ESCC) patients have not been invalidated. This study was designed to determine the prognostic value of EGFR family expression in a population of lymph node-negative ESCC patients treated with curative resection. EGFR family protein expression was examined by immunohistochemical analysis of tissue microarrays of 94 patients with lymph node-negative ESCC after radical esophagectomy with three-field lymphadenectomy. Survival differences were compared using Kaplan–Meier analysis. Cox regression analyses were performed to determine the prognostic factors for overall survival and disease-free survival (DFS). ErbB4 expression was found to be an independent prognostic factor for DFS in patients without lymph node metastasis; increased ErbB4 expression was associated with decreased DFS. Additionally, patients with high ErbB4 expression tended to have worse overall survival. EGFR, ErbB2 and ErbB3 expression were not significantly associated with survival in lymph node-negative ESCC patients. Increased ErbB4 immunohistochemical expression was associated with poor prognosis in lymph node-negative ESCC patients.     

Protein expression and mutational analysis of epidermal growth factor receptor in renal angiomyolipomas

Renal angiomyolipoma (AML) is a benign but progressive tumor that occasionally requires non-surgical therapy and there appears to be a possibility that epidermal growth factor (EGF) is associated with pathogenesis of renal AML. The response to gefitinib, anti-epidermal growth factor receptor (EGFR) agent and a prime example of target therapy, reportedly has been correlated with the presence of mutations within the tyrosine kinase (TK) domain of EGFR or the expression of its truncated form, EGFR variant III. Therefore the purpose of the present paper was to investigate EGFR protein expression and gene mutations in exons 18, 19 and 21 in 40 renal AML. No EGFR gene mutations of TK domain were detected in any of the 40 cases studied and strong immunostaining was found in 5% of the renal AML cases. The present findings indicate that in renal AML, anti-EGFR treatment may not be promising but that there is a possibility that EGFR is associated with renal AML pathogenesis.     

158例肺癌表皮生长因子受体检测及其意义探讨

目的；探讨表皮生长因子受体（ＥＧＦＲ）在肺癌中的表达特征及其临床病理意义。方法：应用ＡＢＣ免疫组织化学法对１５８例肺癌组织进行ＥＧＦＲ检测。结果：非小细胞肺 ＥＧＦＲ阳性率为８０．６％，而小细胞肺癌的ＥＧＦＲ均为阴性，并发现非小细胞肺癌ＥＧＦＲ表达与癌的组织学类型、分化程度、生物行为、肿块大小和临床分期均无相关性。结论：检测肺癌的ＥＧＦＲ有助于鉴别小细胞肺癌和非小细胞肺癌，并认为关于ＥＧＦＲ可能是     

Dependence of activation of the epidermal growth factor receptor on its affinity and oligomerization

R. E. Kavetskii Institute for Problems in Oncology and Radiobiology, Academy of Sciences of the Ukrainian SSR, Kiev. (Presented by Academician of the Academy of Medical Sciences of the USSR A. S. Efimov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 1, pp. 84–87, January, 1992.     

HHV-6和VEGF-C在口腔鳞癌组织中的表达及其相关性

目的探讨人类疱疹病毒6型(HHV-6)和血管内皮生长因子-C(VEGF-C)mRNA及其蛋白表达水平与口腔鳞癌的关系,初步探讨HHV-6感染与VEGF-C表达水平的关系。方法用实时定量PCR技术和免疫组织化学方法检测口腔鳞癌组织中HHV-6和VEGF-C mRNA及其蛋白的表达水平。结果口腔鳞癌组织中HHV-6和VEGF-C mRNA及其蛋白表达水平显著高于正常口腔组织(P0.05);在相同口腔鳞癌组织中HHV-6与VEGF-C mRNA的表达水平显著正相关(P0.001);口腔鳞癌组织中HHV-6和VEGF-C的表达水平与淋巴结转移具有显著相关性(P0.05)。结论口腔鳞癌的发生与HHV-6的感染有关,其感染可能引起VEGF-C的高表达。