Is immunohistochemical epidermal growth factor receptor expression overestimated as a prognostic factor in head-neck squamous cell carcinoma? A retrospective analysis based on a tissue microarray of 365 carcinomas

Epidermal growth factor receptor is overexpressed in more than 80% of head-neck squamous cell carcinoma. Its role as an independent prognostic marker is discussed controversially. No standardized evaluation methods are reported. The aim of our study was to analyze the prognostic relevance of epidermal growth factor receptor expression, using a tissue microarray with more than 300 tumor samples. Epidermal growth factor receptor expression was analyzed by immunohistochemistry and fluorescence in situ hybridization based on a tissue microarray of 365 head-neck squamous cell carcinomas with complete clinicopathologic and follow-up data. Multiple independent observers blinded for clinical data evaluated epidermal growth factor receptor immunostaining semiquantitatively. Cut-off scores for positivity were determined systematically by receiver operating characteristic curve analysis and validated by resampling of the data. Epidermal growth factor receptor expression cut-off scores for loco-regional relapse and overall survival were determined to be 60%. No significant correlation with clinicopathologic data was found. Independent significant differences in loco-regional control and overall survival could not be distinguished by epidermal growth factor receptor expression. Epidermal growth factor receptor expression could not be confirmed as a significant independent prognostic marker in head-neck squamous cell carcinoma using a large tissue microarray with 365 head-neck squamous cell carcinomas with complete clinical data, an evaluation based on immunohistochemistry and fluorescence in situ hybridization by multiple independent observers and systematic determination of cut-off scores.     

Are epidermal growth factor and transforming growth factor responsible for pseudoepitheliomatous hyperplasia associated with granular cell tumors?

Granular cell tumors (GCT) are uncommon benign neoplasms that have a predilection for the head and neck region. These tumors can frequently be associated with pseudoepitheliomatous hyperplasia (PEH), which in turn may be mistaken for squamous cell carcinoma. Although epidermal growth factors are overexpressed in squamous cell carcinomas of the head and neck, their presence in PEH, especially its relation to GCT, is unknown. We hypothesize that the expression of epidermal growth factor receptor (EGFR), epidermal growth factor (EGF), and transforming growth factor alpha (TGFalpha) in GCT have a role in the development of PEH overlying some GCT. Sections from 13 cases of GCT (five with overlying PEH) were examined histologically and evaluated immunohistochemically using monoclonal antibodies for EGFR, EGF, and TGFalpha. These were compared with nine cases of PEH independent of GCT. Two of five GCT with overlying PEH and two of six GCT without overlying PEH stained positively for TGFalpha. None of the GCT stained with EGFR or EGF. All cases of PEH, whether or not associated with GCT, were reactive for EGFR and EGF. Four of the five cases of PEH overlying GCT stained with TGFalpha. The staining pattern and intensity of all three antibodies were comparable to that of the adjacent normal squamous mucosa. Among the three antibodies, only TGFalpha in GCT appears to be related to the development of PEH. Epidermal growth factor receptor and EGF do not seem to be directly involved. The reason of PEH formation associated with GCT in the absence of growth factors is unknown.     

Expression of epidermal growth factor receptor in head and neck cancers correlates with clinical progression: a multicentre immunohistochemical study in the Asia-Pacific region

AIMS: With ongoing efforts to target the epidermal growth factor receptor (EGFR)-mediated tumour growth in the treatment of selected human malignancies, there is a need to determine the expression levels of EGFR and to evaluate its prognostic value in various malignancies in the Asia-Pacific region. METHODS AND RESULTS: A total of 172 patients with head and neck squamous cell carcinomas from Australia, Hong Kong, Singapore, and Taiwan were selected for EGFR detection. Immunohistochemical staining was performed to evaluate EGFR expression. EGFR expression was present in 88.4% (152/172) of all cases tested. Specifically, EGFR expression was found in 91.3% (42/46), 84.6% (22/26), 84.1% (37/44), 96.0% (24/25), and 87.1% (27/31) cases of head and neck squamous cell carcinomas from the oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx, respectively. The results demonstrate a stronger EGFR expression in T4 tumours (P=0.017) and later clinical stages (P=0.016). No significant correlation was seen with risk factors, primary tumour site and ethnicity. CONCLUSIONS: The majority of head and neck squamous cell carcinomas express EGFR, indicating the importance of studying the efficacy of anti-cancer therapy through this pathway. The results also show similar rates of receptor expression in head and neck squamous cell carcinoma patients from our region compared with other parts of the world.     

COX-2 expression correlates with VEGF-C and lymph node metastases in patients with head and neck squamous cell carcinoma.

Recent observations suggest an implication of the cyclooxygenase-2 (COX-2) in tumor lymphangiogenesis through an upregulation of vascular endothelial growth factor-C expression. It is unknown whether this mechanism also acts in squamous cell carcinoma of the head and neck region. We performed a retrospective study of 70 patients with head and neck squamous cell carcinoma in order to investigate whether COX-2 immunohistochemical expression correlates with vascular endothelial growth factor-C expression. We also examined the association of the expression of these molecules with clinicopathologic parameters (especially lymph node status) and outcome for these patients. We performed immunostaining on formalin-fixed, paraffin-embedded tissue sections by the routine streptavidin-biotin peroxidase labeled procedure. Increased cyclooxygenase-2 expression was observed in 30 of the 68 tumor samples (44%), while high vascular endothelial growth factor-C expression occurred in 26 of the 68 tumor samples (38%). High expression of the two proteins was correlated with the presence of lymph node metastasis at the time of diagnosis, and the observed association was even stronger when there was overexpression for both the antibodies (P<0.001). High expression of vascular endothelial growth factor-C, but not of COX-2 was correlated with increased mortality in patients with oral-larynx squamous cell carcinoma. When multivariate Cox regression model was applied, the presence of lymph node metastasis at the time of diagnosis, combined with overexpression of both the antibodies, was the only independent prognostic factor for mortality of these patients. Our results suggest that a lymphangiogenic pathway, in which COX-2 overexpression stimulates vascular endothelial growth factor-C upregulation, probably exists in head and neck squamous cell carcinoma. Also, the predictive ability for mortality of regional lymph node metastasis can be improved with the combined evaluation of the immunohistochemical expression of these two proteins.     

Role of HERG1 potassium channel in both malignant transformation and disease progression in head and neck carcinomas

Evidence indicates that human ether à-go-go-related gene 1 (HERG1) voltage-gated potassium channels could represent new valuable membrane therapeutic targets and diagnostic/prognostic biomarkers in various cancers. This study is the first to investigate the expression pattern of HERG1 potassium channel subunit in both primary tumors and precancerous lesions to establish its clinical and biological role during the development and progression of head and neck squamous cell carcinomas. HERG1 protein expression was evaluated by immunohistochemistry in paraffin-embedded tissue specimens from 133 patients with laryngeal/hypopharyngeal squamous cell carcinomas and 75 patients with laryngeal dysplasia, and correlated with clinical data. Our findings demonstrate that HERG1 is frequently aberrantly expressed in a high percentage of primary tumors (87%), whereas expression was negligible in both stromal cells and normal-adjacent epithelia. HERG1 expression increased during head and neck squamous cell carcinoma progression and was significantly associated with lymph node metastasis (P=0.04), advanced disease stages (P<0.001), regional tumor recurrence (P=0.004), distant metastasis (P=0.03) and reduced disease-specific survival (P=0.012, log-rank test). HERG1-positive expression was also detected in 31 (41%) of 75 laryngeal dysplasias. Interestingly, HERG1 expression increased with the grade of dysplasia; however, HERG1 expression but not histology correlated significantly with increased laryngeal cancer risk (P=0.007). In addition, functional studies in head and neck squamous cell carcinoma-derived cell lines further revealed that HERG1 expression promotes anchorage-dependent and -independent cell growth and invasive capability, although independently of its ion-conducting function. Our data demonstrate that HERG1 expression is a biologically and clinically relevant feature in head and neck squamous cell carcinoma progression and also during malignant transformation, and a promising candidate as cancer risk marker and therapeutic target for head and neck squamous cell carcinoma prevention and treatment.     

Analysis of promoter hypermethylation of death-associated protein kinase and p16 tumor suppressor genes in actinic keratoses and squamous cell carcinomas of the skin.

Death-associated protein kinase is a serine/threonine protein kinase implicated in promoting apoptosis and tumor suppression, whereas p16 is a tumor suppressor gene that inhibits cyclin-dependent kinase 4 and 6 activity and arrests the cell cycle in the G1 phase. Hypermethylation of death-associated protein kinase or p16 gene with resultant gene inactivation has been described in a wide variety of human cancers. Promoter methylation of the death-associated protein kinase and p16 gene has been found in about 55% and 30% cases of head and neck squamous cell carcinoma respectively but has not yet been analyzed in cutaneous premalignant and malignant lesions. A total of 33 cases were examined for evidence of death-associated protein kinase and p16 hypermethylation and these consist of 9 cases of spongiotic dermatitis as nonneoplastic skin control, 9 cases of actinic keratosis, 8 cases of squamous cell carcinoma in situ, and 7 cases of invasive squamous cell carcinoma. Death-associated protein kinase promoter methylation was detected in 1 case of squamous cell carcinoma in situ and 1 case of nonneoplastic skin control but none of the cases of invasive squamous cell carcinoma or actinic keratosis. P16 promoter methylation was detected in 1 case of invasive squamous cell carcinoma and 1 case of nonneoplastic skin control but none of the cases of squamous cell carcinoma in situ or actinic keratosis. Promoter hypermethylation of the death-associated protein kinase and p16 genes does not appear to play an important role in the development of cutaneous squamous cell carcinoma. The data thus suggest that the mechanisms of ultraviolet-induced cutaneous carcinomas differ from those involved in the development of head and neck squamous cell carcinoma, a malignant disease induced by tobacco and alcohol exposure.     

Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and neck squamous cell carcinoma

Prostaglandins play a critical role in tumor development and growth by regulating numerous biologic processes, including tumor angiogenesis, with clear prognostic and therapeutic implications. The aim of this study was to investigate the prognostic relevance of cyclooxygenase-2 (COX-2) pathway activation in head and neck squamous cell carcinoma (HNSCC). COX-2 activity was analyzed in 52 consecutive patients by assessing protein expression and prostaglandin E(2) (PgE(2)) levels and was then correlated to vascular endothelial growth factor (VEGF) expression and tumor angiogenesis. We evaluated the prognostic impact of these parameters by Kaplan-Meier and Cox survival analysis. COX-2 expression by tumor cells was closely correlated to VEGF expression and to tumor vascularization. According to Kaplan-Meier analysis, patients with COX-2 tumor overexpression and with higher PgE(2) tumor levels had significantly shorter overall survival estimates (P = 0.022 and P = 0.033, respectively). Analogously, patients with more-vascularized tumors had worse survival than those with less-vascularized cancers (P = 0.032). Cox multivariate analysis demonstrated that the most significant prognostic factors were presence of lymph node metastasis, tumor vascularization, COX-2 protein expression, and PgE(2) tumor levels. This study demonstrates a close correlation between COX-2 pathway, VEGF expression, and tumor angiogenesis in HNSCC. In addition, COX-2 overexpression and higher tumor vascularization appear to predict a shorter survival in patients with head and neck cancer.     

Molecular biology of laryngeal squamous cell carcinoma

Some of the mechanisms involved in neoplastic transformation and progression of laryngeal squamous cell carcinoma (LSCC) are discussed. Although tumor suppressor inactivation of p53 and p16 is common in these tumors (about 50% each), oncogenic activation is less well characterized. Cyclin D1 and epidermal growth factor receptor amplification have been reported in one-third and one-quarter of LSCCs, respectively, both related to advanced stages, whereas c-myc could be amplified in 13% of cases although without associated overexpression. The role of ras in LSCC is, at most, exceptional, and the role of human papillomavirus infection in these neoplasms could have been largely overestimated. The AIS (amplified in squamous carcinoma) gene has been recently proposed as the main oncogenic target in head and neck squamous carcinomas and is a promising line of investigation. This, along with the link that exists between p53 and INK4 suppressor pathways through ARF and MDM-2, and the role of the universal cdk inhibitors (the Cip/Kip family) in these neoplasms deserve further investigation. Not forgotten are the mechanisms leading to cell immortalization and invasive capabilities acquisition, some of which are also briefly described.     

OVEREXPRESSION OF DIFFERENT MEMBERS OF THE TYPE 1 GROWTH FACTOR RECEPTOR FAMILY AND THEIR ASSOCIATION WITH CELL PROLIFERATION IN PERIAMPULLARY CARCINOMA

The expression of epidermal growth factor receptor (EGFR), c- erb B-2, and c- erb B-3 was examined immunohistochemically in 57 cases of periampullary carcinoma. The percentage of Ki-67-positive cells was also examined in the same tissue, to determine the relationship between the expression of the members of the type 1 growth factor receptor family and cell proliferation. In carcinoma of the head of pancreas, the percentage of cases with overexpression of c- erb B-3 was significantly higher than with overexpression of c- erb B-2 and EGFR. In contrast, in lower bile duct carcinoma and carcinoma of the ampulla of Vater, the percentages of cases with overexpression of c- erb B-2 was greater than with overexpression of other growth factor receptors. A higher percentage of cases with overexpression of c- erb B-3 in pancreatic head carcinoma and overexpression of c- erb B-2 in carcinoma of the ampulla of Vater was found in Ki-67 antigen-positive cases. Moreover, the overexpression of c- erb -3 in pancreatic head carcinoma, c- erb -2 in ampulla of Vater carcinoma, and Ki-67 in both carcinomas was found to be associated with poor patient outcome. These results demonstrate that different members of the type 1 growth factor receptor family are overexpressed in different carcinomas of the periampullary region.     

Overexpression of phosphorylated nuclear factor-kappa B in tonsillar squamous cell carcinoma and high-grade dysplasia is associated with poor prognosis.

Intracellular signals along the epidermal growth factor receptor (EGFR)-Akt-nuclear factor-kappa B (NF-kappaB) pathway have been associated with carcinogenesis in various malignant neoplasms. This investigation was to evaluate the expression of EGFR, phosphorylated(p)-Akt and p-NF-kappaB and correlate them with clinical outcomes in patients with squamous cell carcinoma of the tonsil. A total of 45 patients with squamous cell carcinoma of the tonsil were studied by immunohistochemistry to evaluate the expression levels of EGFR, p-Akt and p-NF-kappaB. Results for squamous cell carcinoma of the tonsil were compared with those for associated high-grade dysplasia and adjacent normal appearing epithelium, when present. In addition, tonsillar epithelium from non-neoplastic specimens of age-matched patients also was stained for the same markers. High-grade dysplasia and squamous cell carcinoma of the tonsil demonstrated a similar pattern of expression, which differed from the pattern seen in the adjacent normal epithelium and tonsillar epithelium from normal controls (an overexpression for each of these three protein analytes in high-grade dysplasia and squamous cell carcinoma of the tonsil as demonstrated by immunohistochemistry). When markers from squamous cell carcinoma of the tonsil were correlated with survival status, only increasing levels of p-NF-kappaB immunoreactivity (a relative overexpression) were statistically significant predictors of poor survival. No markers in squamous cell carcinoma of the tonsil were significantly related to rate of recurrence. When analyzing marker scores from tissue with high-grade dysplasia, relative overexpressions of both p-Akt and p-NF-kappaB were significantly related to poor survival. Additionally, increasing levels of p-NF-kappaB immunopositivity from tissue with high-grade dysplasia were also significantly related to rate of recurrence. In summary, p-NF-kappaB, overexpressed in high-grade dysplasia and squamous cell carcinoma of the tonsil, is associated with worse prognosis in terms of high recurrence and poor survival, respectively. This significant finding in patients with squamous cell carcinoma of the tonsil, in combination with previous animal and in vitro studies, suggests that p-NF-kappaB represents a potential therapeutic target in head and neck squamous cell carcinoma.     

Prognostic significance of stomatin-like protein 2 overexpression in laryngeal squamous cell carcinoma: clinical, histologic, and immunohistochemistry analyses with tissue microarray

Stomatin-like protein 2 (SLP-2) is a novel cancer-related gene whose product promotes cell growth, tumorigenicity, and adhesion in human esophageal squamous cell carcinoma. The purpose of this study was to investigate whether SLP-2 is overexpressed in human laryngeal squamous cell carcinoma (LSCC) and, if so, the significance of its overexpression in relation to clinical parameters. By analyzing 124 cases of LSCC with a tissue microarray, we concluded that SLP-2 is overexpressed in LSCC as compared with the adjacent normal laryngeal epithelium (P = .000) and furthermore that SLP-2 expression correlates with clinical stage. Overexpression can be regarded as a significant prognostic factor, with higher expression being found in lymph node metastasis.     

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.     

Clinicopathologic features of cutaneous squamous cell carcinomas of the head and neck in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma

The clinicopathologic features of 32 cutaneous squamous cell carcinomas of the head and neck in 12 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma were examined to determine the frequency of clinically aggressive and histologically poorly differentiated carcinomas in this group of patients. Two thirds of the neoplasms were multiple and 56% were high grade (grade 3 or 4). One of the 12 patients had recurrent carcinoma, two patients had recurrent and metastatic disease, and two patients had metastatic tumor without recurrence. Two patients died of tumor, one patient is alive with extensive recurrent and metastatic disease, and one patient died of an uncertain type of carcinoma. An additional patient with squamous cell carcinoma of the face died of cutaneous squamous cell carcinoma that arose on the chest. This study shows that cutaneous squamous cell carcinomas of the head and neck in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma are often high grade and have the potential for recurrence and metastasis.     

Detection of EGFR- and HER2-activating mutations in squamous cell carcinoma involving the head and neck.

Recent reports have indicated that mutations in the epidermal growth factor receptor-1 (EGFR) occur in about 7% of patients with squamous cell carcinoma of the head and neck. It is known that many patients with non-small-cell lung cancer who respond to the EGFR inhibitors gefitinib and erlotinib have tumors with EGFR-activating mutations. This might suggest that patients with head and neck squamous carcinoma, who also have tumors with EGFR-activating mutations, might represent a patient population who could benefit from gefitinib or erlotinib therapy. High-resolution melting amplicon analysis (HRMAA) is a recently described technique which can be used for screening tumor DNA isolated from paraffin blocks for tyrosine kinase-activating mutations. In this report we screened 24 cases of squamous cell carcinoma, either primary in the head and neck or secondarily involving the head and neck area, for activating mutations in EGFR exons 18, 19, 20, 21, and for HER2 exons 19 and 20. All cases were followed up by direct DNA sequencing. Two (8%) of the 24 cases were positive. One case was a maxillary sinus tumor which contained an exon 20-activating mutation (N771YinsG). Surprisingly, the other case was a primary squamous cell carcinoma of the skin which invaded the head and neck area only secondarily. This tumor contained an exon 19-activating mutation (G729E). No HER2-activating mutations were found. The presence of a small number of squamous cell carcinomas in the head and neck area with EGFR-activating mutations suggests the existence of a population of patients who could derive benefit from gefitinib or erlotinib therapy. HRMAA could serve as a screening method to easily and rapidly identify these patients.     

Disseminated Mycobacterium chelonae infection in a patient receiving an epidermal growth factor receptor inhibitor for advanced head and neck cancer

We report a case of disseminated cutaneous Mycobacterium chelonae infection in a patient with head and neck cancer on salvage chemotherapy, including the epidermal growth factor receptor inhibitor cetuximab. Mycobacterium chelonae should be considered in the differential diagnosis of cutaneous infections in cancer patients receiving epidermal growth factor receptor inhibitors.     

EGFR and gastrointestinal stromal tumor: an immunohistochemical and FISH study of 82 cases.

Gastrointestinal stromal tumor is the most common mesenchymal neoplasm of the gastrointestinal tract. Mutually exclusive KIT or platelet-derived growth factor receptor-alpha mutations are key events in gastrointestinal stromal tumor pathogenesis, and specific treatment targeting KIT/platelet-derived growth factor receptor-alpha activation is available. Epidermal growth factor receptor plays an important role in cancer biology and also constitutes a promising molecular target of therapy. Very few reports have been published in the literature about the relationship between gastrointestinal stromal tumor and epidermal growth factor receptor. The aim of this study was to investigate epidermal growth factor receptor immunohistochemical expression and epidermal growth factor receptor gene amplification in 82 consecutive gastrointestinal stromal tumor cases using tissue microarray technique. Hematoxylin- and eosin-stained sections and clinical information were reviewed, and expression of CD117 (KIT), CD34 and epidermal growth factor receptor was investigated by immunohistochemistry. Epidermal growth factor receptor gene copy number was determined using fluorescence in situ hybridization. Immunohistochemistry revealed that CD117 and CD34 were expressed in 96 and 57% of tumors, respectively. Variable epidermal growth factor receptor protein immunohistochemical overexpression was detected in 96% of gastrointestinal stromal tumor cases, but none of the 75 cases with represented tumor tissue cores and countable fluorescence signals exhibited epidermal growth factor receptor gene amplification by fluorescence in situ hybridization. These results show that there is no correlation between epidermal growth factor receptor protein overexpression by immunohistochemistry and epidermal growth factor receptor gene amplification by fluorescence in situ hybridization. Considering that the mechanisms of epidermal growth factor receptor protein overexpression are not well understood and the possibility that anti-epidermal growth factor receptor therapy may be beneficial for patients with gastrointestinal stromal tumor that overexpresses epidermal growth factor receptor, additional studies are encouraged.     

Frequent overexpression of multiple ErbB receptors by head and neck squamous cell carcinoma contrasts with rare antibody immunity in patients

In an effort to elucidate the role of ErbB receptors in human head and neck squamous cell carcinoma (HNSCC), expression abnormalities and subcellular localization of epidermal growth factor receptor (EGFR), ErbB2, ErbB3, and ErbB4 were investigated along with EGF and tenascin by immunohistochemistry in 38 carcinomas as compared to adjacent normal mucosa of 24 cases. Although tumour-specific overexpression affected each ErbB receptor (EGFR 47%, ErbB2 29%, ErbB3 21%, ErbB4 26%), EGFR abnormalities were most prevalent. The latter, and overexpression of more than two ErbB receptors in the same tumour, which always included EGFR, correlated with metastatic disease. ErbB products were specifically detected on the cell membrane and in the cytoplasm. In contrast, ErbB4 was uniquely localized to the nucleus in 7 carcinomas and a tumour-derived cell line, indicating a role for regulated intramembrane proteolysis resulting in nuclear ErbB4 translocation in HNSCC. Expression of prototype ligand EGF or low-affinity stromal activator tenascin correlated significantly with EGFR overexpression, implying chronic EGFR activation. Simultaneous overexpression of additional ErbB receptors in most of these cases suggested recurrent involvement of receptor heterodimers. In spite of frequent ErbB receptor alterations, autologous ErbB serum antibodies were rare, with only 1 of 38 tumour patients exhibiting an ErbB2-specific immune response. Based on upregulation of several known immunosuppressive molecules, scarcity of ErbB-specific antibodies is consistent with attenuation of natural tumour-specific immune responses in HNSCC.     

Presence of epidermal growth factor receptor as an indicator of poor prognosis in patients with breast cancer.

Epidermal growth factor receptors are present in some breast cancers in man, and there is an inverse relation to oestrogen receptor state. We assessed the presence of epidermal growth factor receptors as a single prognostic indicator in a series of breast tumours by comparing this with the Bloom and Richardson scores for these tumours. One hundred and eight ductal tumours were examined for epidermal growth factor receptors by radioligand binding. There was a significant (p less than 0.01) correlation between the presence of the growth factor receptor and poor prognosis as assessed by the Bloom and Richardson score, suggesting that epidermal growth factor receptor state could be a useful prognostic marker. Epidermal growth factor receptor state was not significantly correlated with the lymph node state but showed a tendency to be associated with large tumours.     

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.