Expression of human epidermal growth factor and its receptor in esophageal cancer

The expression of human epidermal growth factor (hEGF) was examined immunohistochemically in 86 esophageal cancer lesions, comprising 67 primary tumors and 19 metastatic lymph nodes. In the normal esophagus, the parabasal and intermediate cell layers showed a weak expression of hEGF, however, hEGF-positive tumor cells were detected in 62 (92.5 per cent) of the 67 primary esophageal carcinomas and in 18 (94.7 per cent) of the 19 metastatic lymph nodes. In this study, the immunoreactivity of hEGF was classified into 4 grades according to the number of stained tumor cells. A significant correlation was observed between the histologic type and the grade of hEGF immunoreactivity (Chi-square test, p less than 0.01). hEGF immunoreactivity in well differentiated squamous cell carcinomas was significantly higher than in other squamous cell carcinomas, although there were no correlations between other pathological findings and hEGF immunoreactivity. Patients with hEGF immunoreactivities of grades II or III had much worse prognoses than those with grades 0 or I (p less than 0.05). In 22 esophageal carcinomas and 10 normal esophageal mucosae, EGF receptor (EGFR) contents were measured by the competitive binding assay. The average EGFR content (101.3 +/- 35.7 fmol/mg protein, mean +/- SE) of the esophageal carcinomas was significantly higher than that (5.3 +/- 1.2) of the normal esophageal mucosae (p less than 0.05). Moreover, in hEGF negative tumors, EGFR contents were lower than in hEGF positive tumors. These results suggest that hEGF and EGFR show increased production in squamous cell carcinomas and could to be useful prognostic factors in patients with esophageal cancer.     

The correlation of epidermal growth factor with invasion and metastasis in human gastric cancer

We examined the localization of epidermal growth factor (EGF) in 185 specimens of primary human gastric cancer using the avidinbiotin peroxidase complex immunohistochemical method on formalin-fixed paraffin-embedded sections. Thirty-four per cent of the gastric cancer specimens were positive for EGF, which was mainly located in the cytoplasm of the cancer cells and occasionally in the stromal cells, but was not detected in non-cancerous gastric epithelium. Moreover, the presence of EGF in gastric cancer was correlated with gastric wall invasion and lymph node metastasis. EGF was found more often in advanced cancers than in early ones (p<0.01), and also more often in cancers with lymph node metastasis than in those without (p<0.05). The five-year survival of patients with EGF-positive tumors was worse than that of patients with EGF-negative tumors (p<0.05). The presence of EGF in human gastric cancer may thus represent higher malignant potential.     

Growth fractions of breast cancer in relation to epidermal growth factor receptor and estrogen receptor

Growth fractions detected by a monoclonal antibody, Ki-67, were examined in 40 human breast cancer tissues and the results compared with the immunocytochemical reactivities of epidermal growth factor receptor (EGFR) and estrogen receptor (ER). The proportion of proliferating cells displaying Ki-67 positive staining was significantly higher in the EGFR positive tumors than in the EGFR negative tumors (p<0.01). The average percentage of Ki-67 positive cells in the EGFR positive tumors was 19.9 per cent, whereas that in the EGFR negative tumors was 8.0 per cent. By contrast, an inverse relationship between the proportion of proliferating cells and ER positive cells detected by anti-ER monoclonal antibody was observed. This data indicated the difference in growth fractions with relation to the EGFR and ER status of breast cancer.     

Survival impact of epidermal growth factor receptor overexpression in patients with non-small cell lung cancer: a meta-analysis

BACKGROUND: It is thought that overexpression of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) might compromise patient survival, presumably by promoting tumour growth by an autocrine mechanism. However, conflicting results have been reported from various laboratories, and the clinical importance of EGFR overexpression remains unsettled. METHODS: A meta-analysis of previous studies was performed to quantitatively review the effects of EGFR overexpression on survival in patients with NSCLC using a DerSimonian-Laird random effects model. Eighteen studies including 2972 patients were subjected to final analysis. RESULTS: Overall, positivity for EGFR overexpression differed between histological types: 39% in adenocarcinomas, 58% in squamous cell carcinomas, 38% in large cell carcinomas, and 32% in cancers in a miscellaneous category (p<0.0001). The combined hazard ratio (HR) was 1.14 (95% CI 0.97 to 1.34; p = 0.103), indicating that EGFR overexpression has no significant impact on survival. When only the 15 immunohistochemistry based studies were considered, the combined HR was 1.08 (95% CI 0.92 to 1.28; p = 0.356), again suggesting that EGFR overexpression has no impact on survival. Heterogeneity testing indicated that there was heterogeneity between studies but publication bias was absent, which suggests that the summary statistics obtained may approximate the actual average. CONCLUSIONS: EGFR overexpression was not associated with poorer survival in patients with NSCLC. Specific mutations of the EGFR gene will need further study in terms of survival implications.     

Thymidylate synthase activity,folates, and glutathione system in head and neck carcinoma and adjacent tissues

Background. Head and neck squamous cell carcinomas (HNSCC) present variable aggressiveness and chemosensitivity. Because the glutathione (GSH) system and thymidylate synthase (TS) are involved in the resistance to the main drugs used in HNSCC (cisplatin and 5-FU), we studied these systems in tumors and normal mucosae. Methods. Tumor samples and normal adjacent mucosae were collected from 37 untreated HNSCC patients. GSH and glutathione S-transferase (GST) activity were assayed by spectrophotometry, whereas TS activity and folates were determined by radioassays. Results. Mean GSH levels were higher in tumors (15.2 ± 8.2 nmol/mg protein) than in mucosae (8.3 ± 4.1 nmol/mg protein) (p = 0.005, paired t test). GST activity was also higher in tumors (394 ± 194 nmol/min/mg protein) than in mucosae (261 ± 132 nmol/min/mg protein) (p = 0.0003). TS activity was markedly higher in tumors (9.2 ± 21.5 pmol/min/mg protein) compared to that of mucosae (0.9 ± 1.2 pmol/min/mg protein) (p = 0.0001). Folate levels in tumors and mucosae were similar (1.2 ± 1.1 and 0.8 ± 0.9 pmol/mg protein, respectively; p = 0.1, NS). In relation to clinical stage and tumor size, a statistical difference was found in GSH and GST values between tumors and mucosae for stage IV and T3/T4. The increase in tumor TS compared to that of mucosae was significant for all clinical stages, tumor sizes, and nodal involvement. Conclusions. These data enhance our understanding of the enzymatic systems involved in cisplatin and 5-fluorouracil (5-FU) resistance in HNSCC and normal mucosae and may help to elucidate tumor behavior and interpatient differences in drug sensitivity. © 1994 John Wiley & Sons, Inc.     

膀胱移行细胞癌表皮生长因子及其受体表达和意义

目的 探讨表皮生长因子(EGF)、EGF受体(EGFR)在膀胱移行细胞癌(BTCC)中的表达及意义。方法 用免疫组化ABC法对56例BTCC标本和20例癌旁组织EGF、EGFR进行研究。结果 20例癌旁正常膀胱组织中EGF，EGFR几乎不表达；56例ETCC标本中EGF，EGFR表达明显，与正常组比较有显著性差异(P＜0．01)，不同分期和分级BTCC中的阳性表达率均存在显著性差异(P＜0．05)。结论 EGF，EGFR的检测可以作为判断BTCC预后的一个指标。     

Epidermal growth factor receptor expression correlates with histologic grade in resected esophageal adenocarcinoma

Activation of the epidermal growth factor receptor (EGFR) has a role in oncogenesis and may correlate with prognosis. The aim of this study was to examine EGFR expression in esophageal adenocarcinoma and correlate EGFR status with pathologic and clinical prognostic features. An exploratory retrospective review of 38 patients with surgically resected esophageal adenocarcinoma was performed. All patients underwent an esophagogastrectomy with regional lymphadenectomy; 24 patients underwent primary resection and 14 patients had surgery after preoperative chemoradiation therapy. Immunohistochemical analysis was performed on paraffin-embedded tissue samples using an EGFR monoclonal antibody. Low- and moderate-grade tumors were positive for EGFR expression in 2 of 15 patients; poorly differentiated tumors were positive for EGFR expression in 13 of 23 patients (p = 0.02). The median survival was 35 months (confidence interval [CI]: 29–40) for EGFR negative patients (n = 23) and 16 months (CI: 10–22) for EGFR positive patients (n = 13) (p = 0.10). Disease recurred in 3 of 21 EGFR negative patients and 6 of 13 EGFR positive patients (p = 0.06). Poorly differentiated adenocarcinomas of the esophagus demonstrated higher EGFR expression compared to low-grade tumors based upon immunohistochemical analysis. A trend toward improved disease-free and overall survival was seen in EGFR negative patients.     

Detection of telomerase activity in esophageal squamous cell carcinoma and normal esophageal epithelium

Background/aims: Relatively little has been reported about the telomerase activity of esophageal squamous cell carcinoma or normal esophageal epithelium. In this study, we have evaluated whether telomerase activity is a useful marker for detecting malignancies in the esophagus. Patients/methods: Esophageal carcinomas and normal esophageal tissues adjacent to carcinomas were obtained from 52 surgically treated, unselected patients, and normal esophageal epithelium from 11 non-cancerous patients were obtained by means of biopsy. The telomeric repeat amplification protocol (TRAP) assay was used for detection of telomerase activity in these samples. The incidence of detection of telomerase activity in esophageal carcinoma was compared with that of telomerase activity in normal esophageal epithelium. Moreover, the clinicopathological characteristics of telomerase-positive tumors were compared with those of telomerase-negative tumors. Results: Of the 52 carcinomas, 40 (77%) had detectable telomerase activity. However, telomerase activity was detected in 45 of 52 (87%) normal tissue samples adjacent to carcinomas and in 8 of 11 (73%) normal esophageal epithelium from non-cancerous patients. In esophageal cancer, no significant difference was detected in the clinicopathological findings between the telomerase-positive and -negative cases. Conclusion: These results indicate that not only esophageal squamous cell carcinomas but also normal esophageal epithelium show strong telomerase activity. Thus, telomerase activity may not be a good marker for the detection of carcinoma in the esophagus. Received: 16 March 1999 Accepted: 8 July 1999     

Clinical significance of EGF and EGFR expression changes in cryptorchid boys

Aim: To explore the changes of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) expressions in cryptorchid children and their clinical significance. Methods: The level of serum EGF was measured by radioimmunoassay (RIA) and the expression of EGFR by immunohistochemistry. Results: (1) The level of serum EGF was significantly lower in cryptorchid children than in normal subjects at age group of 59 years (P<0.01) and 10-14 years (P<0.01), (2) The level of EGF was significantly lower in boys with impalpable testis than in those with extracanalicular and intracanalicular testes (P<0.01), (3) The serum EGF level increased significantly 6 months after orchiopexy (P<0.05), (4) The EGFR expression in testicular Leydig's cells was lower in 2-4 year-old boys than in those over 5 years (P<0.05) and (5) the EGFR expression was less positive in the impalpable group and the intracanalicular group than that of the extracanalicular group (P<0.01). Conclusion: The EGF and EGFR expr essions may co     

Gene amplification and overexpression of epidermal growth factor receptor in squamous cell carcinoma of the head and neck.

The degree of gene amplification for epidermal growth factor receptor (EGFR) and its expression levels were examined in 4 cases of tumor lesions and their cell lines of human squamous cell carcinoma (SCC) of the oral cavity. The amplification was detected in 1 case (ZA), but not significantly in 3 other cases (HOC605, HOC815, and HOC927) in which the amplification did not occur during the cell line establishment. In those 3 cases, levels of EGFR synthesis and human EGF (hEGF) binding capacity were varied: HOC605 and HOC815 had slightly increased levels of hEGF binding capacity and EGFR synthesis, respectively. While HOC927 had the lowest levels of both, the hEGF binding capacity was elevated in the tumor lesion when compared with the normal counterpart of the same patient. These results suggest that the increased capacity for EGF binding plays a more important role than does gene amplification on the tumorigenesis of SCC of the head and neck.     

乳腺上皮不典型增生表皮生长因子受体及DNA含量的测定与分析

目的 探讨表皮生长因子受体(EGFR)在乳腺增生症中表达的意义及其与DNA含量的关系。方法 应用免疫组化方法结合图像分析技术对根据Page标准分为三级的44例乳腺增生症(FCD)及28例乳腺浸润性导管癌(IDC)的EGFR表达及DNA含量进行测定，其中二、三级为不典型增生。结果 乳腺增生症Ⅲ级(FCD3)的EGFR表达率最高，其次为FCD2、IDC及FCDl，最低为NMB组，除FCD1与NMB组外，其余相邻组间均有显著性差异(P＜0．05)；在乳腺增生症病例中EGFR阳性病例的DNA含量显著高于EGFR阴性的病例。结论 (1)EGFR过度表达可能是乳腺上皮不典型增生的一个重要特征；(2)EGFR阳性表达的乳腺上皮细胞具有更高的增殖活性。     

TGF-ALPHA IMMUNOREACTIVITY IN LARYNGEAL CARCINOMA: LACK OF PROGNOSTIC VALUE AND CORRELATION TO EGF-RECEPTOR EXPRESSION

Background : Transforming growth factor alpha (TGF-α) is a polypeptide that is structurally similar to epidermal growth factor (EGF) that binds to the epidermal growth factor receptor (EGFR) and has been implicated in the development of several types of human tumours. Methods : The expression of TGF-α is examined in laryngeal squamous cell carcinoma (SCC) (n= 24) and non-neoplastic polyps (n = 7) using streptavidin-biotin immunohistochemistry and a monoclonal antibody to the TGF-α protein. These cases had been previously characterized for EGFR immunoreactivity. The carcinomas were classified as well differentiated (n = 2). moderately differentiated (n = 16) and poorly differentiated (n= 6). Tissues from metastatic tumour deposits in lymph nodes (n = 5) were also studied. Results : TGF-α overexpression was defined as intense immunoreactivity in more than two-thirds of tumour cells immunostained for TGF-a and was present in the majority of the SCC cases (n= 15; 63%) and metastatic turnour deposits (n = 4; 80%). In contrast, although some of the vocal cord polyps showed weak (n= 2) to moderate (n = 5) immunostaining, none had evidence of strong TGF-a immunoreactivity. The differences in TGF-α immunoreactivity were significant between primary laryngeal SCC and vocal cord polyps (P= 0.013; x² test with continuity correction), and between metastatic laryngeal SCC and vocal cord polyps (P = 0.023; x² test with continuity correction). There was no significant difference in TGF-α expression between the different grades of carcinomas (P= 0.92, x² test) or between non-metastatic and metastatic carcinomas (P= 0.82; x² test with continuity correction). No significant correlation was found between TGF-α expression and patient survival or tumour recurrence (r = 0.077, r²= 0.006, P = 0.75; simple regression analysis), or between TGF-α expression and EGFR immunoreactivity (r = 0.325. r'= 0.106, P = 0.0851). Conclusions : In conclusion, increased TGF-α immunoreactivity is present in most cases of laryngeal SCC with no specific relationship to tumour grade, suggesting that it may be important in the development of laryngeal carcinomas but not in its progression. No significant correlation was found between TGF-a and EGFR expression in laryngeal tumours and TGF-a immunoreactivity is of no prognostic value.     

Connective Tissue Growth Factor Gene Expression Alters Tumor Progression in Esophageal Cancer

The ability of cancer cells to initiate specific fibroblast reactions may subsequently determine tumor evolution. In the present study we examined the coordinated expression of transforming growth factor-beta-1 (TGF-b1), its signaling receptors, and its downstream mediator—connective tissue growth factor (CTGF)—and their impact on tumor progression and fibrogenesis in esophageal carcinomas. Messenger ribonucleic acid (mRNA) expression of TGF-b1, CTGF, TGF-b receptor subtype I ALK5 (TbR-IALK5), and TGF-b receptor type II (TbR-II) was studied by Northern blot analysis in esophageal cancer and the normal esophagus. By means of immunohistochemistry and Western blot analysis, the respective proteins were localized in the tissue samples and the protein content was quantitated. Northern blot analysis revealed 3-fold and 4-fold increases (p <0.05) in TGF-b1 and CTGF mRNA levels, respectively, in esophageal cancer in comparison with normal controls, whereas TbR-I mRNA levels were significantly decreased and TbR-II mRNA levels were unchanged in the cancer samples. Immunostaining revealed results similar to those seen on the RNA level. TGF-b1 and CTGF immunoreactivity were increased, TbR-II was unchanged, and TbR-IALK5 immunoreactivity was decreased. CTGF immunoreactivity was mainly present in the stroma surrounding the cancer cells but was also present in the cancer cells. The degree of fibrosis was different in squamous and adenocarcinomas and was significantly related to CTGF mRNA expression levels. The presence of CTGF in squamous cell carcinomas was associated with longer survival, whereas in adenocarcinomas it influenced survival negatively. The findings indicate that TGF-b signaling is disturbed in esophageal cancer. CTGF, a downstream effector of TGF-b action, differentially influences the composition of tumor microenvironment and distinct cell-matrix interactions in the two histological types of esophageal carcinoma, resulting in differences in tumor progression and patient survival.     

Expression of the epidermal growth factor receptor family in normal and malignant urothelium

OBJECTIVE: To compare the immunohistochemically assessed expression of the epidermal growth factor receptor (EGFR) family in normal and malignant bladder urothelium, and suggest new hypotheses about their function in the development and progression of transitional cell carcinoma (TCC). PATIENTS AND METHODS: EGFR, ERBB2, ERBB3 and ERBB4 were evaluated immunohistochemically in normal urothelium (NU, 15), primary non-metastasized invasive TCC (NMC, 19) and in primary invasive TCCs with corresponding metastases (MC, 51, both specimens). RESULTS: All NU samples expressed ERBB4, none expressed ERBB2 and two expressed EGFR; all staining was uniform throughout all cell layers. ERBB2 expression increased and ERBB4 decreased from normal samples to carcinomas. There was no difference between NMCs and MCs in ERBB2, ERBB3 and ERBB4, but the NMCs expressed more EGFR than both NU and MC samples. There were no associations with T category, grade or survival. All combinations of expression levels for the four receptors were detected, with no dominant profile. CONCLUSION: We hypothesise that: (i) ERBB4 is important for differentiation in NU; (ii) ERBB2 is up-regulated with carcinogenesis in the urinary bladder but does not discriminate between bladder cancer with or without metastases; (iii) EGFR may be a marker of indolent disease. A current hypothesis, that superficial layers of NU do not express EGFR and thus protect the basal cells from the mitogenic effect of urinary EGF, is challenged.     

CXCR4/CXCL12信号途径在食管鳞癌浸润转移中的作用机制

目的研究趋化因子受体4(CXCR4)/趋化因子12(CXCL12)信号途径在食管鳞癌浸润转移中的作用机制,为探讨CXCR4成为食管癌治疗新的靶点提供理论依据。 方法取对数生长期的食管鳞癌EC9706细胞,添加趋化因子CXCL12,通过侵袭转移实验、黏附实验分别检测食管鳞癌EC9706细胞株的细胞侵袭、移动和黏附能力。采用RT-PCR和Western Blot技术检测表皮生长因子受体(EGFR)mRNA及蛋白的表达水平。 结果添加不同浓度趋化因子CXCL12(终浓度为5、10 μg/ml),食管鳞癌EC9706细胞株的细胞侵袭、移动和黏附能力均较空白对照组高,并且存在剂量依存关系,即CXCL12浓度越高,细胞的侵袭、移动、黏附能力越强,差异均有统计学意义(P<0.01)。添加不同浓度趋化因子CXCL12,食管鳞癌细胞的EGFR mRNA和蛋白表达水平均较对照组高,并且存在剂量依存关系,即CXCL12浓度越高,EGFR mRNA和蛋白表达水平越高,差异均有统计学意义(P<0.01)。 结论CXCR4/CXCL12信号途径与食管鳞癌细胞的侵袭、转移相关,并且存在剂量依存关系,有可能通过调控EGFR的表达参与食管鳞癌的浸润转移。     

Histological appearance of small thyroid carcinoma

Histopathological characteristics of the tumor growth were studied in 59 small carcinomas detected in thyroids at autopsy and in 33 from surgically removed thyroids. Tumor size was less than 5 mm in 56 of the 59 carcinomas (95 per cent) detected in autopsy materials. Histologic findings of the small carcinomas were papillary adenocarcinoma in 45 of 59 (76 per cent), and sclerosing carcinoma in 32 (54 per cent). Among these 59 small carcinomas, intrathyroid metastases were found in six (10.2 per cent). In small carcinomas measuring less than 5 mm, carcinomas in females had an average diameter of 2.19 mm and were significantly larger than those found in male, having an average diameter of 1.14 mm (p<0.05). In small carcinomas from the surgical specimen, incidence of regional lymph node metastasis was high when associated with numerous intrathyroid metastases and when the distance was great between the edge of the primary tumor and the farthest satellite metastatic focus.     

Impact of pathologically assessing extranodal extension in the thoracic field on the prognosis of esophageal squamous cell carcinoma

BackgroundThis study aimed to elucidate the impact of extranodal extension, pathologically assessed according to new diagnostic criteria, on the prognosis of esophageal squamous cell carcinoma. Extranodal extension has been shown to be a prognostic indicator for head and neck cancers; however, its utility in esophageal squamous cell carcinoma has not been demonstrated.MethodsWe enrolled 174 consecutive esophageal squamous cell carcinoma patients who had undergone esophagectomy with lymph node dissection in the three fields. Extranodal extensions from all metastatic lymph nodes were pathologically classified into grades 1–3. Then, relationships between extranodal extension and clinicopathologic factors, including overall survival and recurrence-free survival were examined. Recurrence patterns in the thoracic and abdominal fields were also examined.ResultsKaplan–Meier analyses showed that patients with grades 2 and 3 extranodal extension showed significantly poorer recurrence-free survival compared with those with intranodal involvement of esophageal squamous cell carcinoma cells (P = .0041 and P = .0011, respectively). Patients with pN3b (newly defined in this study as including at least one lymph node with grade 2–3 extranodal extension regardless of region or number of metastatic lymph nodes) was associated with significantly shorter overall survival and recurrence-free survival (P < .001). Moreover, multivariate analyses indicated that patients with grades 2–3 extranodal extension showed significantly reduced recurrence-free survival in the thoracic but not in the abdominal field (thoracic: P = .047; abdominal: P = .15).ConclusionThis study suggests that the extranodal extension grading system proposed in this study is a novel predictor of overall survival and recurrence-free survival in esophageal squamous cell carcinoma.     

Metastatic Brain Tumours from Oesophageal Carcinoma: Neuro-Imaging and Clinicopathological Characteristics in Japanese Patients

Summary  Background. Since metastatic brain tumours from esophageal carcinoma are essentially rare, previous reports have not determined the common neuro-radiological findings and its clinical aspects.  Findings. We report the neuro-imaging and clinicopathological features of our 8 metastatic brain tumours from an esophageal site. Histologically, 6 of our 8 patients had squamous cell carcinoma and 2 had small cell carcinoma, a rare variant form. Both histological types mainly exhibited cystic lesions with a thin enhanced rim on magnetic resonance images (MRI, 4 of 6 squamous cell carcinomas and 1 of 2 small cell carcinomas). Combination therapy (irradiation and chemotherapy) after surgical treatment, the number of metastatic brain tumours, and the interval between their appearance and the diagnosis of the primary lesion could be prognostic factors in our series.  Interpretation. Among Japanese, the vast majority of primary esophageal cancers are squamous cell carcinomas. Therefore, MRI findings of a cystic tumour with a thin enhanced rim may alert one to the possibility of a metastatic brain tumour from the esophagus.     

Podoplanin is a highly sensitive and specific marker to distinguish primary skin adnexal carcinomas from adenocarcinomas metastatic to skin

Distinction of primary skin adnexal carcinomas from cutaneous metastasis of adenocarcinomas is challenging. In this study, we evaluated podoplanin immunoreactivity in a series of primary skin adnexal tumors and adenocarcinomas metastatic to skin using a D2-40 antibody. The initial test series were composed of a total of 93 cases including 32 primary skin adnexal carcinomas, 46 benign primary adnexal tumors, and 15 cutaneous metastatic adenocarcinomas. We found that variable D2-40 reactivity was seen in all of the primary cutaneous carcinomas including sebaceous carcinomas (10/10), squamous cell carcinomas (10/10), porocarcinomas (4/4), trichilemmal carcinomas (4/4), skin adnexal carcinomas not otherwise specified (4/4), and in the majority of benign skin adnexal tumors. In contrast, no podoplanin immunoreactivity was seen in any of the 15 (0/15) cutaneous metastases. To confirm the initial findings and to further explore the utility of podoplanin reactivity in the distinction of these tumors, we also examined a test set of 35 unknown cases, including 21 adenocarcinomas metastatic to skin and 14 primary adnexal tumors, in a blinded fashion. In this test set of cases, podoplanin was negative in 22 cases and positive in 13 cases. Of the 22 podoplanin negative cases, 20 were proven to be metastatic adenocarcinoma. Of the 13 D2-40 positive cases, 12 were proven to be primary adnexal tumors. Our results suggest that podoplanin can be a useful tool to distinguish primary skin adnexal carcinomas form adenocarcinomas metastatic to skin with high sensitivity (94.5%) and specificity (97.2%).     

Evaluation of malignancy and the prognosis of esophageal cancer based on an immunohistochemical study (p53, E-cadherin, epidermal growth factor receptor)

The subjects in this study consisted of 40 preoperative untreated esophageal squamous cell carcinoma patients. While p53 did not significantly correlate with the clinicopathological factors, E-cadherin significantly correlated with lymphatic invasion, vascular invasion, the depth of invasion, the degree of lymph node metastasis, the histological stage, and the number of lymph node metastases. Epidermal growth factor receptor (EGFR) significantly correlated with age, the depth of invasion, and the number of lymph node metastases. The 5-year cumulative survival rate was 45.7% in the p53-positive cases and 61.9% in the p53-negative cases, with no significant difference, and 87.8% in the E-cadherinpositive cases and 19.1% in the-negative cases, and the difference was significnat. The prognosis was significantly poor in EGFR-positive subjects: the 5-year survival rate was 38.6% in EGFR-positive cases and 68% in-negative cases. The 5-year survival rate in E-cadherin-negative, EGFR-positive cases was 0%, while it was 91.7% in the reverse pattern, and this difference was significant. These findings suggest that both E-cadherin and EGFR are important prognostic factors, and a more precise prognosis can thus be obtained by combining them. Such a combined technique may be very useful as an indicator for grading the biological malignancy of esophageal cancer.