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HER-2/neu Expression (her-2/neu + expression)
Selected AbstractsHER-2/neu expression in extramammary Paget disease: a clinicopathologic and immunohistochemistry study of 47 cases with and without underlying malignancyJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2009Jose A. Plaza Extramammary Paget disease (EMPD) is an infrequent skin cancer sometimes representing a secondary event caused by extension of an underlying carcinoma. Her-2/neu overexpression in breast cancer is correlated with a more aggressive behavior, but anti-Her-2/neu therapy improves survival in these patients. We investigated Her-2/neu expression by immunohistochemistry in cases of EMPD with and without underlying malignancy to try to correlate with tumor recurrence, progression and possible targeted therapy. Forty-seven cases were analyzed (6 from the scrotum, 7 perianal region, 1 axilla and 33 vulva). Two cases had invasive EMPD (one from vulva and one from scrotum). The overall Her-2/neu expression was 31.9%. Of the noninvasive EMPD of the vulva (32 cases), Her-2/neu was shown in 38%. The case of invasive vulvar EMPD was negative. All six scrotal EMPD lacked Her2/neu expression. Her-2/neu was expressed in two of seven perianal cases (33.3%). The EMPD on the axilla (one case) was negative. Eighteen cases had recurrence, and of these, 44.4% expressed Her-2/neu in the initial lesion. A high proportion of EMPD showed Her-2/neu expression (31.9%), indicating that these patients may benefit from targeted therapy. The proportion of positive cases was higher in lesions that had recurred at last follow up (44.4%), suggesting a more aggressive behavior. [source] BS12 PREDICTIVE MARKERS FOR BREAST CANCER NEOADJUVANT CHEMOTHERAPYANZ JOURNAL OF SURGERY, Issue 2007S. Syed Purpose Although neoadjuvant chemotherapy (NACT) is routinely used in the management of breast cancer, there is no definitive way of predicting which patients are more likely to respond to a particular therapy. The aim of this study was to identify markers that can be used to predict tumor response to chemotherapy in breast cancer. Methodology We used immunohistochemistry to evaluate blood microvessel density (MVD) (CD31), tumor cell proliferation (Ki-67), anti-apoptotic marker (Bcl-2), ER and PR expression, and HER-2/neu expression in core biopsy samples (taken before chemotherapy) from patients with locally advanced breast cancer (n = 20), receiving neo-adjuvant chemotherapy {anthracycline-based regimen (FEC100) (n = 10) vs single agent taxane regimen (docetaxel) (n = 10), and correlated these factors with tumor response (as assessed clinically and by tumor imaging) after 4 cycles of treatment. Results Tumors expressing low levels of Bcl-2 showed significantly greater reduction in size to both taxane (P < 0.05) and anthracycline-based (P < 0.01) regimens, compared to tumors expressing high levels of Bcl-2. Further, HER-2/neu positive tumors showed significantly greater reduction in size to taxane regimen (P < 0.05), while estrogen receptor (ER) negative tumors showed a trend of greater reduction in size to anthracycline-based regimen (P = 0.06). Conclusions Bcl-2 and HER-2/neu expression may be useful markers to predict response to neoadjuvant chemotherapy in breast cancer. While subject numbers are still too low to draw firm conclusions, the current data indicates that HER-2/neu may specifically predict a positive tumor response to taxane regimen, and high Bcl-2 is a marker of chemoresistance. [source] HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinomaCANCER, Issue 11 2005Peter A. Learn M.D. Abstract BACKGROUND The use of biologic markers to predict response to neoadjuvant chemotherapy may permit tailoring regimens to achieve maximal tumor response. Taxanes have demonstrated excellent activity in breast carcinoma; however, tumor-specific factors that predict clinical response have not been characterized thoroughly. METHODS The authors performed a historic review evaluating the association of tumor prognostic factors and response to neoadjuvant cyclophosphamide and doxorubicin (AC) with or without docetaxel (D) (AC vs. AC+D) in 121 women who previously were enrolled in a Phase III, randomized, clinical trial. Using pretreatment biopsy materials, immunohistochemical studies were performed for estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, p53, and Ki-67. Outcome variables were pathologic complete response (pCR) and positive clinical response (cPOS), which was defined as a , 50% regression in clinical tumor size prior to surgery. RESULTS In a multivariate analysis that controlled for tumor size and lymph node status, improved cPOS rates were observed with the addition of docetaxel in women with HER-2/neu -negative tumors (81% vs. 51%; P < 0.05), yielding an adjusted odds ratio of 3.5 (95% confidence interval, 1.2,13.0) in favor of docetaxel. Women who had HER-2/neu -negative tumors appeared to have a lower response rate with AC alone compared with women who had HER-2/neu -positive tumors (51% vs. 75%; P = 0.06), but response rates were matched when docetaxel was added (81% vs. 78%; P = 0.99). ER, PR, p53, and Ki-67 results were not associated significantly with response rates. CONCLUSIONS HER-2/neu status may predict improved clinical response rates from the addition of docetaxel to anthracycline-based neoadjuvant chemotherapy. Docetaxel may "rescue" the response in women who have HER-2/neu -negative tumors to match that observed in women who have HER-2/neu -positive tumors treated with AC alone. Cancer 2005. © 2005 American Cancer Society. [source] Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/neu in synovial sarcoma,CANCER, Issue 4 2005Dafydd G. Thomas M.D., Ph.D. Abstract BACKGROUND Synovial sarcomas are high-grade soft tissue neoplasms often characterized by a biphasic spindle and epithelioid cell morphology. The majority of synovial sarcomas harbor a specific chromosomal translocation in which the proximal portion of the SYT gene at chromosome 18q11 is fused to the distal portion of one of several duplicated SSX genes (most notably SSX1 and SSX2) at chromosome Xp11. SYT/SSX1 translocations are seen in nearly three times as many synovial sarcomas as SYT/SSX2 translocations. Although the SYT/SSX2 fusion is usually associated with the monophasic disease pattern, the SYT/SSX1 fusion is present in tumors with biphasic or monophasic patterns. The SYT/SSX1 fusion gene is associated with more aggressive tumor growth and poor outcome. Despite advances in the therapy of local disease, distant metastasis remains the predominant cause of death. Accordingly, there is a need for alternate therapies, such as those recently developed against the receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and HER-2/neu. METHODS Archival specimens of synovial sarcoma (n = 38) representing 30 patients were assessed for EGFR and HER-2/neu protein expression by standard immunohistochemical techniques. To validate the immunohistochemistry results, quantitative real-time polymerase chain reaction (Q-PCR) assays using either fresh and/or archival material was performed. The presence of gene amplification was determined by chromogenic in-situ hybridization. RESULTS EGFR and HER-2/neu protein were detected by immunohistochemistry in 21 of 38 (55.3%) and 20 of 38 (52.6%) synovial specimens, respectively. EGFR immunoreactivity showed a granular and membranous pattern, whereas HER-2/neu immunoreactivity demonstrated only a membrane pattern. Coexpression was observed in 13 of 38 specimens (34.2%). HER-2/neu expression by immunohistochemistry in synovial sarcomas was restricted to tumors with the SYT/SSX1 translocations. Of 6 specimens with SSX2 translocation, none (0%) showed HER-2/neu immunoreactivity and 1 (17%) demonstrated EGFR expression. Q-PCR demonstrated the presence of mRNA for EGFR and HER-2/neu in 19 of 30 specimens (63.3%) and 22 of 30 specimens (73.3%), respectively. EGFR and HER-2/neu were expressed at low concentrations compared with the expression of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). No evidence of gene amplification was observed. CONCLUSIONS EGFR and HER-2/neu are expressed in the majority of patients with SYT/SSX1 synovial sarcomas, albeit at low levels. Treatment with tyrosine kinase inhibitors may represent appropriate alternate therapy for these patients. Cancer 2005. © 2005 American Cancer Society. [source] Androgen receptors frequently are expressed in breast carcinomasCANCER, Issue 4 2003Potential relevance to new therapeutic strategies Abstract BACKGROUND Several studies have demonstrated the biologic and therapeutic significance of estrogen and progesterone receptors (ER and PR) in breast carcinomas. The aim of the current study was to examine the presence of androgen receptors (AR) in breast carcinomas. METHODS Two hundred cases of breast carcinoma, consisting of 145 invasive and 55 noninvasive (ductal carcinoma in situ [DCIS]) lesions, were examined using a monoclonal antibody against AR on formalin-fixed, paraffin-embedded archival material. The results were analyzed for correlations with immunohistochemically determined ER, PR, and HER-2/neu expression. RESULTS Eighty-seven of the 145 cases (60%) of invasive carcinoma and 45 of the 55 cases (82%) of DCIS were AR-positive according to internationally standardized guidelines. The vast majority of Grade 1 carcinomas were positive for AR (90% of invasive Grade 1 carcinomas and 95% of Grade 1 DCIS), whereas in Grade 3 invasive carcinomas and DCIS, positive immunoreactions for AR were observed in 46% and 76% of cases, respectively. Among the cases of Grade 3 carcinoma, 33 invasive carcinomas (39%) and 17 DCIS lesions (68%) were ER-negative but AR-positive. Among Grade 1 carcinomas (invasive and DCIS), not a single case was positive for HER-2/neu, but most cases were intensely positive for AR. In contrast, many invasive Grade 3 carcinomas exhibited agreement between AR status and HER-2/neu status (AR-positive and HER-2/neu-positive, 30.5%; AR-negative and HER-2/neu-negative, 42.5%). CONCLUSIONS Androgen receptors are commonly expressed in DCIS and in invasive breast carcinoma. A significant number of poorly differentiated carcinomas are ER-negative and PR-negative but AR-positive. Immunohistochemical examination of AR would be desirable because it would provide additional information about steroid receptors in breast carcinomas. Cancer 2003;98:703,11. © 2003 American Cancer Society. DOI 10.1002/cncr.11532 [source] Evaluation of HER-2/neu expression in prostatic adenocarcinomaCANCER, Issue 8 2002A request for a standardized, organ specific methodology Abstract BACKGROUND Some evidence suggests a role for HER-2/neu overexpression in prostate carcinoma progression. Reported rates of HER-2/neu overexpression in patients with prostate carcinoma vary greatly. METHODS The authors studied radical prostatectomy specimens from 38 patients who had biochemical failure after undergoing radical prostatectomy for prostate carcinoma. Immunohistochemistry for HER-2/neu overexpression using the HercepTest kit (Dako Corporation, Carpenteria, CA) was employed. Two different antigen-retrieval techniques were used: 1) the standard U.S. Food and Drug Administration (FDA)-approved HercepTest assay and 2) a modified HercepTest, which employed an alkaline citrate buffer, pH 9.0, for antigen retrieval and a 1-hour primary antibody incubation time. The level of HER-2/neu expression was evaluated on a scale from 0 (no staining) to 3+ according to the published guidelines. Fluorescent in situ hybridization for gene amplification was performed on all specimens. RESULTS With the standard technique, only one specimen had 2+ staining, and no specimens had 3+ staining. With the modified technique, 10 specimens (26%) had 2+ staining, and 9 specimens (24%) had 3+ staining. There was a significant association between the level of HER-2/neu expression shown with the modified technique and tumor stage (P = 0.03) as well as Gleason grade (P = 0.01). None of the specimens had HER-2/neu gene amplification. CONCLUSIONS The authors report a simple modification of the HercepTest that resulted in an increased rate of HER-2/neu expression, which was correlated with poor-risk pathologic findings. The findings suggest that adenocarcinoma of the prostate should be evaluated for HER-2/neu expression with a prostate specific immunohistochemical procedure that differs from the FDA-approved standard procedure. Cancer 2002;95:1650,5. © 2002 American Cancer Society. DOI 10.1002/cncr.10839 [source] Interrelationships between Cellular Nucleotide Excision Repair, Cisplatin Cytotoxicity, HER-2/neu Gene Expression, and Epidermal Growth Factor Receptor Level in Non-small Cell Lung Cancer CellsCANCER SCIENCE, Issue 2 2000Chun-Ming Tsai Nucleotide excision repair (NER) is a major repair mechanism for DNA lesions induced by cisplatin. Overexpressions of epidermal growth factor receptor (EGFR) and HER-2/neu have been reported to affect the sensitivity of certain human cancer cells to cisplatin, presumably by modification of DNA repair activity through interference with NER. Using an in vitro repair assay, we investigated NER activity of cisplatin-induced DNA lesions in a panel of 16 non-small cell lung cancer (NSCLC) cell lines. The interrelationships between NER activity, cisplatin sensitivity, HER-2/neu expression and EGFR level, were also analyzed. The results showed that high NER activity was closely correlated with cisplatin resistance and high levels of HER-2/neu expression (P < 0.05). Analysis of the relationships between EGFR level and each of the other three parameters revealed no statistically significant correlations (all P values were > 0.05 by Spearman rank correlation), but a trend of association (all the values of proportion of accordance were ,62.5% by using a 2x2 contingency table). These results suggest that NER activity may play an important role in the cisplatin resistance of NSCLC cells and there may be an association between enhanced NER activity and high levels of p185neu and probably EGFR in NSCLC cells. The finding that high levels of EGFR showed very little influence on the relationship between p185neu and cisplatin resistance suggests that EGFR may be a less crucial factor in modulating the chemoresistance of NSCLC cells when compared with HER-2/neu. [source] HER-2/neu expression in extramammary Paget disease: a clinicopathologic and immunohistochemistry study of 47 cases with and without underlying malignancyJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2009Jose A. Plaza Extramammary Paget disease (EMPD) is an infrequent skin cancer sometimes representing a secondary event caused by extension of an underlying carcinoma. Her-2/neu overexpression in breast cancer is correlated with a more aggressive behavior, but anti-Her-2/neu therapy improves survival in these patients. We investigated Her-2/neu expression by immunohistochemistry in cases of EMPD with and without underlying malignancy to try to correlate with tumor recurrence, progression and possible targeted therapy. Forty-seven cases were analyzed (6 from the scrotum, 7 perianal region, 1 axilla and 33 vulva). Two cases had invasive EMPD (one from vulva and one from scrotum). The overall Her-2/neu expression was 31.9%. Of the noninvasive EMPD of the vulva (32 cases), Her-2/neu was shown in 38%. The case of invasive vulvar EMPD was negative. All six scrotal EMPD lacked Her2/neu expression. Her-2/neu was expressed in two of seven perianal cases (33.3%). The EMPD on the axilla (one case) was negative. Eighteen cases had recurrence, and of these, 44.4% expressed Her-2/neu in the initial lesion. A high proportion of EMPD showed Her-2/neu expression (31.9%), indicating that these patients may benefit from targeted therapy. The proportion of positive cases was higher in lesions that had recurred at last follow up (44.4%), suggesting a more aggressive behavior. [source] | ||||||||||