PCNA expression in cutaneous keratinous neoplasms and verruca vulgaris.

Using an antibody to PCNA and a standard immunohistochemical system, the authors examined normal epidermis and cutaneous neoplasias for expression of PCNA, a protein associated with DNA polymerase delta and DNA replication. In squamous cell carcinoma in situ (SCCI), a unique expression of PCNA, which frequently involved the nuclei of all keratinocytes within the lesion, was found. Heaviest staining was in the uppermost layers of the epidermis. PCNA expression ended abruptly at the histologic margin of the lesion. Because SCCI can be associated with the presence of human papillomavirus (HPV) DNA, the authors evaluated PCNA expression in verruca vulgaris and found a pattern similar to that in SCCI. Assuming that PCNA expression in these two lesions is related to cell division, the authors hypothesize that the mechanisms that control proliferation in SCCI may be similar to those operative in verruca vulgaris.     

Fatty acid synthase expression in cutaneous melanocytic neoplasms.

Mammalian fatty acid synthase is a multifunctional enzyme complex involved in de novo synthesis of saturated fatty acids, and inhibitors of fatty acid synthase are being evaluated as potential therapeutic agents. Increased fatty acid synthase expression has been demonstrated in subsets of malignancies, including colon, breast, endometrium, prostate and ovarian carcinomas, and recently malignant melanomas. We evaluated the immunohistochemical expression of fatty acid synthase in 155 cutaneous melanocytic lesions. They included 30 congenital nevi, 19 compound nevi, 40 Spitz nevi, 48 primary melanomas, and 18 metastatic melanomas. Fatty acid synthase expression was stronger in malignant melanomas in comparison to conventional nevi and Spitz nevi, and was the highest for metastatic melanoma. Of the primary malignant melanomas, mean fatty acid synthase scores were significantly greater for Clark levels IV and V compared to Clark levels I and II (P<0.001). In addition, melanomas with Breslow thickness 0.75-1.50 mm and >1.50 mm showed significantly higher mean fatty acid synthase scores compared with those with Breslow thickness <0.75 mm (P=0.013 and <0.001, respectively). Of interest, congenital melanocytic nevi also showed strong fatty acid synthase expression, similar to that seen in metastatic melanoma. This may represent persistence of or regression to a fetal phenotype since normal fetal tissues are known to express high levels of fatty acid synthase.     

CD10在皮肤附属器肿瘤中的表达及在区分皮肤转移性肾细胞癌鉴别诊断中的潜在作用

外科病理诊断中肿瘤发生皮肤转移并不少见，其提示肿瘤复发或发生结外扩散。某些恶性肿瘤如肾细胞癌发生皮肤转移的临床症状可能会导致皮肤原发性恶性肿瘤的诊断。有3％～11％肾细胞癌可发生皮肤转移，而皮肤转移性肾细胞癌的形态学特点与皮肤原发的附属器肿瘤特别是具有透明细胞分化者难以鉴别。为了确定CD10在各种皮肤附属器病变中的表达以及其在区分转移性肾细胞癌中的价值，作者研究了57例原发性附属器肿瘤，其中小汗腺分化31例，大汗腺分化16例，皮脂腺分化10例、正常皮肤3例和4例皮肤转移性肾细胞癌。结果发现CD10表达于正常皮肤的皮脂腺，小汗腺和大汗腺上皮表达阴性，而汗腺周围的肌上皮细胞表达CD10。     

S100A6 expression in cutaneous smooth muscle neoplasms

The S100A6 protein is expressed in a variety of tissues and distinct staining patterns in S100A6 immunohistochemistry may be useful in the differential diagnosis of difficult lesions. We evaluated the staining pattern of the S100A6 antibody in 22 cases each of pilar leiomyoma (LM), angioleiomyoma (ALM), and cutaneous leiomyosarcoma (LMS). S100A6 labeled both the nucleus and cytoplasm of myocytes in positive cases. About 64% of LM and 86% ALM had positive staining to the S100A6 antibody but predominantly in a weak staining pattern. In contrast, 95% of the LMS exhibited moderate to strong staining with the S100A6 antibody. The difference in the frequency of positive cases was statistically significant in the LM vs LMS comparison (p = 0.025), but we found intensity of staining to be of greatest practical utility. Analysis between the groups taking in to consideration differences in intensity of staining using the nonparametric rank sum (Mann–Whitney U test) demonstrated that there was a statistically significant difference between LM and LMS and between ALM and LMS. Weak or absent S100A6 staining supports a diagnosis of LM, whereas strong positive staining supports a diagnosis of LMS.     

Summary of expression of SPARC protein in cutaneous vascular neoplasms and mimickers

BackgroundSerum protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein, which regulates cell proliferation and facilitates intracellular transport of albumin bound particles including chemotherapeutic agents such as Nab-paclitaxel/ABI-007. Therefore the presence of SPARC may achieve higher intra-tumoral drug concentration with lower dosage and thus reduce systemic side-effects. Several trials of ABI-007, in melanoma, show promising clinical activity.DesignFifty-four cases of dermal based neoplasms were retrieved including 24 angiosarcomas (AS), 10 hemangiomas, 9 nodular melanomas, 4 Kaposi sarcomas (KS), 3 leiomyosarcomas (LMS), 3 atypical fibroxanthomas (AFX) and 1 spindle cell squamous cell carcinoma (SSCC). SPARC immunohistochemistry (IHC) was performed with a mouse monoclonal antibody.ResultsSPARC expression was detected in a majority of AS (17/24), melanomas (8/9), AFX (3/3), LMS (3/3) and KS (4/4) with some expression in hemangiomas (3/10), while being negative in SSCC (0/1); and was significantly associated with tumor group (p = 0.017). Although a significant difference in overall survival was observed between SPARC expression groups (positive vs. negative) for all patients, there was no significant difference noted among angiosarcoma patients.ConclusionWe have confirmed the presence of SPARC expression in melanoma, KS, LMS and AS and also detected it for the first time in AFX. Since paclitaxel has shown some effectiveness in AS, melanoma and KS, ABI-007 could also be beneficial in these patients.     

PTEN和Her-2表达与乳腺癌长期预后的关系

目的:探讨PTEN及Her-2在人原发性乳腺癌组织中表达的临床意义及其对术后生存时间的影响。 方法:应用免疫组化法检测81例有15年可靠随访资料的乳腺癌石蜡标本中Her-2和PTEN的表达。采用卡方检验，Kaplan Meier法及Log－rank检验， Cox模型回归分析等方法分析PTEN及Her-2在原发性乳腺癌组织中单独表达及共表达的临床意义。 结果:(1)PTEN表达显著影响乳腺癌患者术后5年和10年的生存率（P<0.01和P<0.05）；PTEN表达与Her-2显著负相关（P<0.01）；(2)PTEN阴性合并Her-2阳性表达患者的5年和10年生存率显著低于PTEN阳性合并Her-2阴性表达的患者；(3)肿瘤大小、术后辅助治疗和PTEN的表达可以作为影响5年生存率有意义的风险因素（P<0.05），而ER、Her-2和PTEN的表达可以作为影响10年生存率有意义的风险因素（P<0.05）。 结论: PTEN与Her-2表达可以影响乳腺癌术后生存率，Her-2和PTEN的表达可以作为分子标记物判断乳腺癌的预后。     

Her-2 protein expression, cellular localization, and gene amplification in colorectal carcinoma.

This study was sought to evaluate the relationship between Her-2 protein expression, cellular localization, gene amplification, and other clinicopathologic parameters in colorectal carcinomas. Her-2 protein expression and gene amplification were assessed in paraffin sections from 106 primary colorectal adenocarcinoma cases using immunohistochemistry and fluorescence in situ hybridization. Both membranous and cytoplasmic immunostaining was evaluated. The results were correlated with each other and with tumor grade, stage, and overall survival. Membranous and cytoplasmic protein expression was identified in 6 (5.6%) and 13 (12.26%) cases, respectively. Gene amplification was detected in 4 (3.7%) cases. There was a high concordance between membranous protein expression and gene amplification (kappa=0.791). No apparent association with any of the clinicopathologic parameters was identified. Membranous Her-2 protein expression and gene amplification are encountered in a small subset of colorectal carcinomas and are highly concordant events. Cytoplasmic protein expression might be either artifactual or it might represent a cross-reacting protein or a precursor form of the mature protein.     

Cyclooxygenase-2 expression in normal ovaries and epithelial ovarian neoplasms.

Cyclooxygenase-2 (COX-2) expression was investigated immunohistochemically in 57 epithelial ovarian neoplasms and in histologically normal ovaries. Positive immunostaining for COX-2 was observed in 78.6% (22/28) of the ovarian cancers and in 66.7% (14/21) of the borderline-malignant tumors. The rate of expression was significantly higher among the ovarian cancers than the benign cystadenomas (4/8; 50%) (p<0.05). There was a significant correlation between vascular endothelial growth factor (VEGF) expression and microvessel count (MVC), but no correlation between COX-2 expression and MVC. There was a significant correlation between VEGF expression and COX-2 expression in all of the ovarian neoplasms as a whole (p<0.05). These findings suggest that an increase in COX-2 expression may be associated with malignant transformation and tumorigenesis of epithelial ovarian neoplasms.     

Cyclooxygenase-2 expression in thyroid neoplasms

AIMS: Previous studies have demonstrated that cyclooxygenase-2 (COX-2) plays a role in carcinogenesis and carcinoma development. In this study, we investigated its expression in thyroid neoplasms in order to elucidate its role. METHODS AND RESULTS: COX-2 expression was studied immunohistochemically in 20 anaplastic (undifferentiated) carcinomas, 49 papillary carcinomas, 22 follicular carcinomas and 15 follicular adenomas. Positive staining was only occasionally seen in normal follicles or stromal cells. COX-2 over-expression was found in only 20.0% of follicular adenomas and 40.9% of follicular carcinomas. In papillary carcinomas, the incidence (81.3%) was significantly higher (P < 0.0001) than in follicular carcinomas, although COX-2 expression was reduced in cases with old age (P = 0.0190), large size (P = 0.0028), advanced stage (P = 0.0225), satellite tumours (P = 0.0363), and the presence of solid, scirrhous or trabecular growth patterns (P = 0.0018). Undifferentiated carcinomas less frequently over-expressed COX-2 (P = 0.0004), with an incidence of 40.0%. CONCLUSIONS: These results indicate that the up-regulation of COX-2 may contribute predominantly in the early phase of papillary carcinoma progression, whereas it plays a more adjuvant role in follicular carcinoma progression.     

Her-2/neu and breast cancer.

Breast cancer is the most common malignancy in women in the United States in the year 2000. The proto-oncogene Her-2/neu (c-erb-B2) has become an increasingly important prognostic and predictive factor in breast cancer. Overexpression/amplification of the Her-2/neu has been associated with a worse outcome in patients with breast cancer. Herceptin, a "humanized" murine monoclonal antibody directed against the extracellular domain of the Her-2/neu protein, is being used to treat breast cancer that overexpresses Her-2/neu. The status of Her-2/neu in the tumor has become a critical factor in the management strategy of a breast cancer patient. The objective of this article is to provide a comprehensive review of all aspects of Her-2/neu in breast cancer, including biology, prognostic and predictive value, targeted Herceptin therapy, and the laboratory testing of Her-2/neu.     

Retinoblastoma expression in thyroid neoplasms.

Retinoblastoma (Rb) mutation in thyroid neoplasia has been identified in a few molecular studies; however, the utility of Rb immunohistochemistry in distinguishing benign and malignant thyroid lesions has not been documented in formalin-fixed, paraffin-embedded tissues. The present study investigated Rb immunohistochemistry in a series of 111 formalin-fixed, paraffin-embedded benign and malignant thyroid lesions. All of the major histologic subtypes were included to detect any heterogeneity in Rb-1 expression that might influence the diagnostic utility of this technique or further elucidate the pathogenesis of thyroid neoplasia among the categories. Altogether, 34 follicular adenomas, 9 follicular carcinomas, 7 Hürthle cell adenomas, 5 Hürthle cell carcinomas, 23 papillary carcinomas (8 of which were follicular variants), 4 insular carcinomas, 4 anaplastic carcinomas, 6 medullary carcinomas, and 19 nodular goiters were analyzed. Avidinbiotin immunohistochemistry was performed using the Dako Rb-1 clone. Pronase digestion was introduced into the epitope retrieval protocol to eliminate false-positive cytoplasmic stainig. Nuclear immunoreactivity was assessed as positive if 10% or more of thyroid epithelial nuclei stained positively, and conversely as negative. The majority of benign non-Hürthle thyroid lesions, whether hyperplastic or neoplastic, retained Rb nuclear immunopositivity in most cells (51 of 53 cases [96%]). Conversely, malignant thyroid neoplasms lacked Rb immunoreactivity in the majority (42 of 51 cases [82%]), including all papillary carcinomas (23 of 23) and almost all follicular carcinomas (8 of 9 [89%]). Virtually all Hürthle cell neoplasms were negative (11 of 12 [92%]), whether benign or malignant. In conclusion, Rb immunohistochemistry can aid in the distinction between benign and malignant thyroid lesions in conjunction with morphology. This seems to be most applicable to the often problematic differentiation between follicular adenoma and the follicular variant of papillary carcinoma (P < .0001; sensitivity and specificity, 100%) or minimally invasive follicular carcinoma (P = .0007; sensitivity, 89%; specificity, 100%).     

Her-2/neu, Ki-67 expression and ploidy in breast carcinoma

Expression of the markers was studied immunocytochemically on cytological preparations of breast tumor, ploidy was assessed by flow cytofluorimetry. The material was divided into 2 groups: diploid--41.4% cases and aneuploid--58.6%. Hyperexpression of Her-2/neu in the first group was observed in 54.5%, in the 2nd group in 48.6% cases. Expression of Ki-67 in 63.4% and in 68.9%, respectively. Tumours with high proliferative activity were numerous in aneuploid tissues, and in diploid tumours moderate activity prevailed (p = 0.006). Direct correlation between the markers was observed, high expression of Ki-67 more frequently was associated with positive expression of Her-2/neu. Thus, aneuploid tumours with high proliferative activity and hyperexpression of Her-2/neu are more aggressive tumours of a large size.     

Cytokeratin expression in epithelioid vascular neoplasms.

Seven epithelioid and eight non-epithelioid vascular tumors were studied by the avidin-biotin-peroxidase method for the presence of endothelial- and epithelial-associated markers, using Ulex europaeus agglutinin-1 (UEA-1) lectin, and antibodies directed against factor VIII-related antigen, (FVIII-RA), vimentin, keratin, carcinoembryonic antigen, and epithelial membrane antigen. The cases included four epithelioid hemangiomas, two epithelioid hemangioendotheliomas (EHE), one epithelioid angiosarcoma (EAS), four common non-epithelioid capillary hemangiomas, and four non-epithelioid angiosarcomas. Staining for FVIII-RA, UEA-1, and vimentin were observed in all cases. The EAS showed staining for keratin in formalin-fixed, paraffin-embedded sections and in frozen sections. Staining for keratin was also observed in frozen sections of one EHE. Both keratin-positive vascular tumors were confirmed with electron microscopy. Carcinoembryonic antigen and epithelial membrane antigen stains were negative in all cases. Our results show that the epithelioid vascular tumors EHE and EAS, in addition to staining for the endothelial markers and vimentin, may also express the epithelial marker keratin. This is important since these tumors may closely resemble carcinomas by routine light microscopy. This study further underscores the importance of using a broad panel of immunohistochemical markers in the diagnostic workup of soft-tissue neoplasms.     

Her-2/neu expression in salivary duct carcinoma: an immunohistochemical and chromogenic in situ hybridization study.

Salivary duct carcinoma (SDC) shares significant morphologic and immunophenotypic overlap with ductal carcinoma of the breast, including HER-2/neu expression. Previous studies have detected HER-2/neu at the protein level in SDCs; however, no study, to date, has assayed whether this expression is related to gene amplification detected by chromogenic in situ hybridization (CISH). Formalin-fixed, paraffin-embedded tissue sections from 12 previously diagnosed SDCs were evaluated by immunohistochemistry (IHC) and CISH for HER-2/neu status. Result concordance was seen in all 12 cases. A total of 4 SDCs were positive by IHC; all 4 cases showed amplification with CISH. The remaining 8 cases were negative by IHC and showed no gene amplification with CISH. SDCs in this study show HER-2/neu overexpression on both the protein and gene levels in approximately 30% of cases. These findings suggest a role may exist for Herceptin (trastuzumab) based therapy in some SDC patients.