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Biomedical subjects

Allen M Gown

Publications and source records attributed to Allen M Gown.

At least 19 recordsLinked to original sources
PubMed2007

Nonsmall cell lung carcinoma with neuroendocrine differentiation--an entity of no clinical or prognostic significance.

The existence of non-small cell lung carcinoma with neuroendocrine differentiation as a distinct entity and its relevance for prognostic and treatment purposes is controversial. This study assesses the frequency and biologic and prognostic significance of neuroendocrine (NE) expression of synaptophysin (SNP), chromogranin (Ch), and neural cell adhesion molecule (N-CAM) using tissue microarray (TMA) and immunohistochemistry. Six hundred nine nonsmall cell lung carcinomas (NSCLCs) were reviewed for subclassification. TMA blocks were made using duplicate 0.6-mm-diameter tissue cores and slides stained with SNP, Ch, and N-CAM. Immunoreactivity was considered if 1% or more of tumor cells were positive. Hematoxylin and eosin-stained sections were subclassified as: 243 adenocarcinoma (ACA), 272 squamous cell carcinoma (SCC), 35 large cell carcinoma, 32 non-small cell carcinoma NOS, and 6 other (carcinosarcoma, giant cell carcinoma). Positivity for either marker was identified in 13.6% of NSCLC (76/558). NSCLC showed reactivity for Ch in 0.4% of cases (2/524), for SNP in 7.5% of cases (39/521) and for N-CAM in 8.6% of cases (44/511), whereas only 0.2% of cases (1/517) showed coexpression of SNP and Ch and none of all 3 markers. The assessment of NE differentiation in NSCLC is unnecessary and expensive and is of no clinical or prognostic significance. SNP or N-CAM stains a small minority of NSCLC, whereas Ch immunoreactivity is less common. Positivity for any 2 NE markers is rare. SNP is more likely to be expressed in adenocarcinoma (P=0.01) and N-CAM in squamous-cell carcinoma (P=0.008). Otherwise there was no correlation between immunoreactivity and tumor morphology. Disease specific and overall survival is not influenced by NE differentiation and therefore non-small cell lung carcinoma with neuroendocrine differentiation should not be a subclass distinct from the other NSCLC.

Biomarkers, Tumor↗
PubMed2006

Immunohistochemical detection using the new rabbit monoclonal antibody SP1 of estrogen receptor in breast cancer is superior to mouse monoclonal antibody 1D5 in predicting survival.

PURPOSE: Estrogen receptor (ER) expression predicts improved breast cancer-specific survival and reduced risk of recurrence and is targeted in breast cancer therapy. A high-quality antibody to identify ER-positive patients plays an important role in clinical decision making for women with breast cancer. This study evaluates immunohistochemistry using two anti-ER antibodies, a new rabbit monoclonal antibody (SP1) and the mouse monoclonal antibody (1D5), in relation to biochemical ER assay results and clinical data on survival and adjuvant systemic therapy. PATIENTS AND METHODS: A population-based tissue microarray series of 4,150 invasive breast cancers was constructed. All patients had staging, pathology, treatment, and follow-up information. The median follow-up was 12.4 years and the median age at diagnosis 60 years. Survival analysis and log-rank tests were used to evaluate the prognostic value of ER status and correlations with clinical data. RESULTS: Among the 4,105 samples interpretable for both antibodies, SP1 detected ER positivity in 69.5% and 1D5 in 63.1% of cases. Both monoclonal antibodies are demonstrated to be good prognostic indictors for breast cancer-specific and relapse-free survival. In multivariate analysis, including age, tumor size, grade, and lymphovascular and nodal status, SP1 was a better independent prognostic factor than 1D5. Among patients with discrepant ER results, the 8% of patients who were SP1 positive/1D5 negative showed good outcomes, and the 2% SP1-negative/1D5 positive had poor outcomes. Maintaining the same 92% specificity and 98% positive predictive value, SP1 is 8% more sensitive than 1D5 using biochemical assay as gold standard. CONCLUSION: SP1 represents an improved standard for ER immunohistochemistry assessment in breast cancer.

Animals↗
PubMed2006

Immunohistochemical expression of CDX2 in primary ovarian mucinous tumors and metastatic mucinous carcinomas involving the ovary: comparison with CK20 and correlation with coordinate expression of CK7.

Recent studies have demonstrated conflicting results regarding the value of CDX2 for distinguishing primary ovarian mucinous tumors from metastatic mucinous carcinomas in the ovary. Utility of coordinate expression of cytokeratins 7 and 20 is restricted to distinction of ovarian mucinous tumors from lower gastrointestinal tract metastases and data comparing coordinate expression of all three markers is limited. Immunohistochemical studies were performed to compare expression of CDX2 and cytokeratin 20, both markers of intestinal differentiation, in conjunction with coordinate expression of cytokeratin 7, in 90 mucinous tumors involving the ovary: 42 primary ovarian mucinous tumors (31 atypical proliferative (borderline) mucinous tumors (gastrointestinal type), 11 mucinous carcinomas) and 48 metastatic mucinous carcinomas of upper (pancreaticobiliary tract: 14; stomach: five) and lower (colon and rectum: 25; appendix: four) gastrointestinal tract origin. Primary ovarian tumors expressed CDX2 (40%) less frequently than cytokeratin 20 (83%) (P<0.0001). CDX2 expression in primary ovarian tumors (40%) was lower than CDX2 expression in metastatic carcinomas of both upper (74%; P=0.016) and lower gastrointestinal tract origin (90%; P<0.0001). Cytokeratin 20 expression was similar in primary ovarian tumors (83%) and metastases of upper (89%; P=0.071) and lower gastrointestinal tract origin (93%; P=0.29). Thus, as a single marker CDX2 offers some advantage over cytokeratin 20 because it is less frequently positive in primary ovarian tumors. In the almost universally cytokeratin 7-positive primary ovarian tumors and metastases of upper gastrointestinal tract origin, CDX2 coordinate expression was less common in primary ovarian tumors (36%) than in metastases of upper gastrointestinal tract origin (63%) (P=0.022) whereas cytokeratin 20 coordinate expression was identical in both tumor types (79%). In the almost universally cytokeratin 7-negative metastases of lower gastrointestinal tract origin, coordinate expression of CDX2 (83%) and cytokeratin 20 (86%) were equivalent (P=1.00). CDX2 was comparable to cytokeratin 20 in distinguishing metastases of lower gastrointestinal tract origin (usually cytokeratin 7-negative and CDX2/cytokeratin 20 positive) from primary ovarian tumors and metastases of upper gastrointestinal tract origin (usually cytokeratin 7-positive and CDX2/cytokeratin 20 variable). CDX2 provided some advantage over cytokeratin 20 for distinguishing primary ovarian mucinous tumors from metastases of upper but not lower gastrointestinal tract origin; however, the advantage in the former was limited due to the occurrence of shared coordinate expression profiles in both tumor types. Cytokeratin 7 provides the predominant discriminatory value among these markers yet is limited to distinction of primary ovarian tumors from metastases of lower gastrointestinal tract origin.

Adenocarcinoma, Mucinous↗
PubMed2006

Immunohistochemistry for estrogen and progesterone receptors in the distinction of primary and metastatic mucinous tumors in the ovary: an analysis of 124 cases.

Estrogen (ER) and progesterone receptor (PR) expression in primary ovarian mucinous tumors and the utility of these markers for distinguishing metastatic mucinous carcinomas in the ovary from primary ovarian mucinous tumors have not been extensively investigated. Immunohistochemical studies were performed on 124 mucinous tumors, including 52 primary ovarian tumors (30 atypical proliferative (borderline) mucinous tumors of gastrointestinal type, 11 atypical proliferative (borderline) mucinous tumors of seromucinous (endocervical-like) type, and 11 invasive mucinous carcinomas of usual (gastrointestinal) type) and 72 metastatic mucinous carcinomas in the ovary (primary sites: colorectum (24), pancreas (13), endocervix (eight), stomach (four), gallbladder/bile duct (four), appendix (four), and unknown (15)). All atypical proliferative mucinous tumors of gastrointestinal type, primary ovarian mucinous carcinomas, and metastatic mucinous carcinomas were negative for ER and PR with the exception of three metastatic endocervical adenocarcinomas which exhibited only weak expression of ER without PR. All atypical proliferative mucinous tumors of seromucinous type expressed ER to some degree and seven had some expression of PR. Immunohistochemical assessment of hormone receptor expression is of no value in distinguishing the common types of primary ovarian mucinous tumors (atypical proliferative mucinous tumors of gastrointestinal type and mucinous carcinomas of usual type) from the vast majority of mucinous carcinomas metastatic to the ovary. The above observations on hormone receptor expression in primary ovarian mucinous tumors support the concept that atypical proliferative (borderline) mucinous tumors of gastrointestinal and seromucinous (endocervical-like) types are distinctive tumors.

Adenocarcinoma, Mucinous↗
PubMed2006

Evaluation of 12 antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma: identification of a three-antibody immunohistochemical panel with maximal sensitivity and specificity.

We evaluated the sensitivity and specificity of 10 monoclonal and two polyclonal antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma (AdCA) using immunohistochemistry (IHC). The antibodies were directed against the mesothelial-associated antigens mesothelin, calretinin, cytokeratin 5, thrombomodulin, Wilms' tumor-1 (WT-1) gene product and HBME-1, and the nonmesothelial antigens Lewis-Y blood group (antibody BG8), MOC-31, BerEp4, CD15, and carcinoembryonic antigen (CEA) family. The 133 tumors evaluated included 65 malignant epithelioid mesotheliomas, 22 lung AdCAs, 27 ovarian serous carcinomas, 24 breast carcinomas, and five gastric carcinomas. Diagnoses were based on clinical, histologic, ultrastructural, and/or IHC findings. Calretinin had the best sensitivity for mesothelioma (95%), followed by HBME-1 (84%), WT-1 (78%), cytokeratin 5 (76%), mesothelin (75%), and vimentin and thrombomodulin (68%). Thrombomodulin had the best specificity for mesothelioma (92%), followed by cytokeratin 5 (89%), calretinin (87%) vimentin (84%), and HBME-1 (45%). When ovarian carcinomas were excluded from the analysis, the specificity of mesothelin and WT-1 for the diagnosis of mesothelioma increased to 90 and 81%, respectively. The sensitivity of the nonmesothelial antigens for AdCA was organ dependent, with BG8 performing best in the breast cancer group (96%), and BerEp4, BG8, MOC-31 performing best in the lung cancer group (100%). The specificity of the nonmesothelial antigens for AdCA was 98% for BG8 and CEA, 97% for CD15, 95% for BerEp4, and 87% for MOC-31. A novel statistical analysis technique employing logic regression analysis identified a three-antibody immunohistochemical panel including calretinin, BG8, and MOC-31, which provided over 96% sensitivity and specificity for distinguishing epithelioid mesothelioma from AdCA.

Adenocarcinoma↗
PubMed2006

Intracystic papillary carcinomas of the breast: a reevaluation using a panel of myoepithelial cell markers.

Intracystic papillary carcinomas (IPC) of the breast have traditionally been considered to be variants of ductal carcinoma in situ (DCIS). However, it is not clear if all lesions categorized histologically as IPC are truly in situ carcinomas, or if some such lesions might represent circumscribed or encapsulated nodules of invasive papillary carcinoma. Given that the demonstration of a myoepithelial cell (MEC) layer around nests of carcinoma cells is a useful means to distinguish in situ from invasive carcinomas of the breast in problematic cases, assessment of the presence or absence of a MEC layer at the periphery of the nodules that comprise these lesions could help resolve this issue. We studied the presence and distribution of MEC at the periphery of the nodules of 22 IPC and, for comparison, 15 benign intraductal papillomas using immunostaining for 5 highly sensitive markers that recognize various MEC components: smooth muscle myosin heavy chain, calponin, p63, CD10, and cytokeratin 5/6. All 22 lesions categorized as IPC showed complete absence of MEC at the periphery of the nodules with all 5 markers. In contrast, a MEC layer was detected around foci of conventional DCIS present adjacent to the nodules of IPC. Furthermore, all benign intraductal papillomas, including those of sizes comparable to those of IPC, showed a MEC layer around virtually the entire periphery of the lesion with all 5 MEC markers. In conclusion we could not detect a MEC layer at the periphery of the nodules of any of 22 lesions categorized histologically as IPC. One possible explanation for this observation is that these are in situ lesions in which the delimiting MEC layer has become markedly attenuated or altered with regard to expression of these antigens, perhaps due to their compression by the expansile growth of these lesions within a cystically dilated duct. Alternatively, it may be that at least some lesions that have been categorized as IPC using conventional histologic criteria actually represent circumscribed, encapsulated nodules of invasive papillary carcinoma. Regardless of whether these lesions are in situ or invasive carcinomas, available outcome data indicate that they seem to have an excellent prognosis with adequate local therapy alone. Therefore, we believe it is most prudent to continue to manage patients with these lesions as they are currently managed (ie, similar to patients with DCIS) and to avoid categorization of such lesions as frankly invasive papillary carcinomas. Given our observations, we favor the term "encapsulated papillary carcinoma" over "intracystic papillary carcinoma" for circumscribed nodules of papillary carcinoma surrounded by a fibrous capsule in which a peripheral layer of MEC is not identifiable.

Aged↗
PubMed2006

Cytokeratins 7 and 20 in primary and secondary mucinous tumors of the ovary: analysis of coordinate immunohistochemical expression profiles and staining distribution in 179 cases.

Coordinate expression profiles for cytokeratins 7 and 20 (CK7 and CK20) are useful for distinguishing certain types of adenocarcinomas but use for distinction of primary and secondary mucinous tumors in the ovary is limited due to the existence of a number of tumor types exhibiting overlapping CK7/CK20 immunoprofiles; the use of staining distribution patterns in the distinction of tumors with shared profiles has not been evaluated in detail. We report analysis of both coordinate expression profiles and staining distribution in 179 rigorously classified mucinous tumors in the ovary, including 53 primary tumors [35 atypical proliferative (borderline) mucinous tumors of gastrointestinal type and 18 invasive mucinous carcinomas] and 126 secondary tumors [28 colorectal adenocarcinomas, 54 appendiceal tumors (23 adenocarcinomas, 31 low-grade adenomatous mucinous tumors associated with pseudomyxoma peritonei), 14 pancreatic adenocarcinomas, 8 endocervical adenocarcinomas, 5 gastric adenocarcinomas, 4 gallbladder/biliary tract adenocarcinomas, and 13 adenocarcinomas of unknown primary sites). A CK7+/CK20+ immunoprofile was the most common profile in primary ovarian tumors (74%), upper gastrointestinal tract tumors (78%), and endocervical tumors (88%) but was occasionally observed in lower intestinal tract tumors (colorectal: 11%; appendiceal: 13% of low-grade tumors, 35% of carcinomas). A CK7-/CK20+ immunoprofile was the most common profile in lower intestinal tract tumors (79%) and was uncommon in upper gastrointestinal tract tumors (9%), rarely seen in primary ovarian tumors (4%), and not seen in endocervical tumors. A CK7+/CK20- profile was observed in some primary ovarian (23%), upper gastrointestinal tract (13%), and endocervical tumors (13%) but not in lower intestinal tract tumors. For CK7+ tumors, staining distribution was very frequently diffuse (>50% of tumors cells positive) in primary ovarian, upper gastrointestinal tract, and endocervical tumors, whereas staining distribution was often focal (<50% of tumors cells positive) when present in colorectal and appendiceal carcinomas but not in low-grade appendiceal tumors. For CK20+ tumors, staining distribution was variable but often focal in primary ovarian tumors and nonlower intestinal tract tumors, whereas the pattern was almost always diffuse in lower intestinal tract tumors. Immunohistochemical staining distribution can supplement CK7/CK20 coordinate expression profiles to distinguish subsets of primary ovarian and metastatic lower intestinal tract mucinous tumors having overlapping immunoprofiles but neither coordinate expression profiles nor staining distribution distinguishes primary ovarian tumors from the nonlower intestinal tract metastases.

Adenocarcinoma↗
PubMed2006

Ovarian atypical proliferative (borderline) mucinous tumors: gastrointestinal and seromucinous (endocervical-like) types are immunophenotypically distinctive.

Ovarian atypical proliferative (borderline) mucinous tumors of gastrointestinal and seromucinous types are considered subtypes within the mucinous tumor category despite the presence of distinctive clinicopathologic features that seromucinous tumors share with pure serous tumors. Immunophenotypic differences have not been extensively investigated. Immunohistochemical studies were performed to compare the expression patterns of cytokeratins 7 and 20 (CK7, CK 20), estrogen and progesterone receptors (ER, PR), CA-125, mesothelin, and WT-1 in 28 tumors of gastrointestinal type and 12 tumors of seromucinous type. Both gastrointestinal and seromucinous type tumors had a high frequency of CK7 expression (93% and 100%, respectively). The gastrointestinal type tumors were characterized by frequent expression of CK20 (86%) and CDX2 (39%), infrequent expression of CA-125 (11%) and mesothelin (7%), and lack of expression of ER, PR, and WT-1. In contrast, the seromucinous type tumors were characterized by frequent expression of ER (100%), PR (67%), CA-125 (92%), and mesothelin (83%), infrequent expression of WT-1 (8%), and lack of expression of CK20 and CDX2. The gastrointestinal and seromucinous types of atypical proliferative mucinous tumors are immunophenotypically distinctive tumors. The former are characterized by expression of markers of gastrointestinal-type differentiation (CK20 and CDX2), whereas the latter are characterized by expression of "müllerian-type" markers (ER, PR, CA-125, and mesothelin). Expression of the latter markers in the seromucinous tumors, which also are expressed in pure serous tumors, and lack of expression of gastrointestinal-type markers, combined with the clinicopathologic features these tumors share with pure serous tumors, support the concept that this subtype is more closely related to serous than gastrointestinal type mucinous tumors and justify the designation "seromucinous."

Adenocarcinoma, Mucinous↗
PubMed2005

Vaginal lymphatic channel location and its implication for intracavitary brachytherapy radiation treatment.

PURPOSE: In vaginal intracavitary brachytherapy using cylindrical applicators, it is common to prescribe dose to a depth of 0.5 cm to cover the lymphatic channels. However, the actual depth of the lymphatics within the vaginal wall has never been determined. In this study, we examined the depth distribution of lymphatics lying beneath the mucosal surface of the vagina. METHODS AND MATERIALS: Between January 24, 1996 and October 27, 2003, 31 patients underwent full-thickness vaginal biopsy or partial resection for both benign and malignant disease. In addition, in February 2004, vaginal samples from two autopsy specimens were stretched and pinned for formalin fixation and slide production. Forty-five slides of both stretched and nonstretched vaginal tissue were stained with D2-40 monoclonal antibody lymphatic endothelium marker. The percentages of lymphatics located within 1, 1-2, 2-3, and 3-4mm were calculated for all slides. RESULTS: For the nonstretched samples, the percentages of lymphatics located within 1, 1-2, 2-3, and 3-4mm were 50.5%, 30.7%, 11.9%, and 6.9%, respectively. For the stretched samples, the percentages of lymphatics located within 1, 1-2, 2-3, and 3-4mm were 44.0%, 33.8%, 18.8%, and 3.4%, respectively. The differences of lymphatic percentages within and superficial to 1mm (p=0.60), 1-2mm (p=0.85), 2-3mm (p=0.89), and 3-4mm (p=0.99) were not statistically significant between the stretched and nonstretched states. CONCLUSIONS: Our results show that approximately 95% of vaginal lymphatic channels are located within a 3mm depth from the vaginal surface. This suggests that dose prescribed to a depth less than 0.5 cm may be adequate and could permit treatment with less normal tissue toxicity in certain clinical situations.

Adult↗
PubMed2005

Nuclear beta-catenin in mesenchymal tumors.

Beta-catenin is a crucial part of the Wnt and E-cadherin signalling pathways, which are involved in tumorigenesis. Dysregulation of these pathways allow beta-catenin to accumulate and translocate to the nucleus, where it may activate oncogenes. Such nuclear accumulation can be detected by immunohistochemistry, which may be useful in diagnosis. Although the role of beta-catenin has been established in various types of carcinomas, relatively little is known about its status in mesenchymal tumors. A number of studies suggest that beta-catenin dysregulation is important in desmoid-type fibromatosis, as well as in synovial sarcoma. We wished to determine whether nuclear beta-catenin expression is specific to and sensitive for particular bone and soft-tissue tumors, including sporadic desmoid-type fibromatosis. We studied the nuclear expression of beta-catenin using tissue microarrays in a comprehensive range of bone and soft-tissue tumor types. A total of 549 cases were included in our panel. Nuclear immunohistochemical staining was determined to be either high level (>25% of cells), low level (0-25%) or none. High-level nuclear beta-catenin staining was seen in a very limited subset of tumor types, including desmoid-type fibromatosis (71% of cases), solitary fibrous tumor (40%), endometrial stromal sarcoma (40%) and synovial sarcoma (28%). Although occasional cases of fibrosarcoma, clear cell sarcoma and carcinosarcoma had high-level staining, no high-level nuclear beta-catenin expression was seen in any of 381 fibrohistocytic, muscular, adipocytic, chondroid or osseous tumor cases representing 42 diagnostic categories. All primary immunostain tissue microarray images are made publicly accessible in a searchable database. High-level nuclear beta-catenin staining serves as a useful diagnostic tool, as it is specific to a small subset of mesenchymal tumors.

Cell Nucleus↗
PubMed2005

Fluorescence in situ hybridization for the detection of t(X;18)(p11.2;q11.2) in a synovial sarcoma tissue microarray using a breakapart-style probe.

Synovial sarcomas (SSs) account for 5% of soft tissue tumors and carry a balanced translocation t(X;18)(p11.2;q11.2), detectable in over 90% of cases. This translocation brings together portions of two genes: SYT and SSX. Detecting interruption of the SYT gene on chromosome 18 would be useful as a diagnostic tool. We describe a scoring method to detect disruption of SYT with breakapart probe fluorescence in situ hybridization (FISH) and the application of this method for identification of SS within a sarcoma tissue microarray. After optimization, SYT disruption was identified in 22 of 23 (96%) of known SS tumor samples but was not in 23 of 23 (100%) of non-SS sarcoma samples. Ten of 11 (91%) blinded test SS tumor samples were also correctly identified. For comparison, commercially available FISH and chromogenic in situ hybridization (CISH) probes were tested. The commercial FISH probes identified SYT disruption in 81% of the SS tumor samples but in none of the non-SS samples. The CISH probes produced signals too weak to interpret. The use of breakapart FISH probes is a relatively quick procedure for detection of synovial sarcoma translocations and can be applied to archival specimens in tissue microarrays.

Chromosomes, Human, Pair 11↗
PubMed2004

Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma.

PURPOSE: Expression profiling studies classified breast carcinomas into estrogen receptor (ER)+/luminal, normal breast-like, HER2 overexpressing, and basal-like groups, with the latter two associated with poor outcomes. Currently, there exist clinical assays that identify ER+/luminal and HER2-overexpressing tumors, and we sought to develop a clinical assay for breast basal-like tumors. EXPERIMENTAL DESIGN: To identify an immunohistochemical profile for breast basal-like tumors, we collected a series of known basal-like tumors and tested them for protein patterns that are characteristic of this subtype. Next, we examined the significance of these protein patterns using tissue microarrays and evaluated the prognostic significance of these findings. RESULTS: Using a panel of 21 basal-like tumors, which was determined using gene expression profiles, we saw that this subtype was typically immunohistochemically negative for estrogen receptor and HER2 but positive for basal cytokeratins, HER1, and/or c-KIT. Using breast carcinoma tissue microarrays representing 930 patients with 17.4-year mean follow-up, basal cytokeratin expression was associated with low disease-specific survival. HER1 expression was observed in 54% of cases positive for basal cytokeratins (versus 11% of negative cases) and was associated with poor survival independent of nodal status and size. c-KIT expression was more common in basal-like tumors than in other breast cancers but did not influence prognosis. CONCLUSIONS: A panel of four antibodies (ER, HER1, HER2, and cytokeratin 5/6) can accurately identify basal-like tumors using standard available clinical tools and shows high specificity. These studies show that many basal-like tumors express HER1, which suggests candidate drugs for evaluation in these patients.

Biomarkers, Tumor↗
PubMed2004

HER-2 testing in breast cancer using parallel tissue-based methods.

CONTEXT: Testing for HER-2 oncogene in breast cancer has increased because of its role as a prognostic and predictive factor. Some advocate gene testing by fluorescence in situ hybridization (FISH) vs protein testing by immunohistochemistry as the method which most accurately evaluates and predicts response to the anti-HER-2 antibody, trastuzumab. However, critical examination of FISH on a screening basis has yet to be performed. OBJECTIVES: To determine the correlation between FISH and immunohistochemistry results by determining HER-2/neu gene status on tumor sections with indeterminate immunohistochemistry results (2+ score), confirm gene amplification on tumor sections with positive results (3+ score), and verify gene status on tumor sections with negative results (0 or 1+ score). DESIGN, SETTING, AND PATIENTS: A quality control and quality assurance program for HER-2 testing by FISH, which used tumor specimens from 2963 patients (median age, 56 years) with breast cancer received from 135 hospitals and cancer centers in 29 states, was performed at a reference laboratory from January 1, 1999, to May 15, 2003. Every specimen evaluated by FISH was parallel tested with immunohistochemistry tests. MAIN OUTCOME MEASURES: With FISH as the presumed standard testing method, the positive and negative predictive values and sensitivity and specificity of immunohistochemistry were calculated. RESULTS: A total of 3260 clinical HER-2 tests by FISH were performed on 2963 serially referred breast cancer specimens. Of these, 2933 tests were successful and 2913 breast cancer specimens had both FISH and immunohistochemistry results available. With FISH as the standard testing method, the positive predictive value of positive immunohistochemistry score (3+) was 91.6%, and the negative predictive value of negative immunohistochemistry score (0 or 1+) was 97.2%. The sensitivity of immunohistochemistry tests, including tumor sections with scores of 2+ or 3+, was 92.6% and the specificity of immunohistochemistry tests with scores of 3+ was 98.8%. The FISH test had a significantly higher failure rate (5% vs 0.08%) and reagent cost (140 dollars vs 10 dollars), and longer testing (36 hours vs 4 hours) and interpretation times (7 minutes vs 45 seconds) vs immunohistochemistry tests. CONCLUSIONS: A testing algorithm for HER-2 determination is most efficient by using immunohistochemistry as the method of choice, with FISH performed for cancers with indeterminate results (2+ score). Successful quality control and quality assurance programs are a prerequisite for such approaches.

Adult↗
PubMed2004

Wilms tumor gene product: sensitive and contextually specific marker of serous carcinomas of ovarian surface epithelial origin.

Carcinomas of ovarian surface epithelial origin can arise from, and often present at, extraovarian sites. There are few available markers for the positive identification of carcinomas of ovarian surface epithelial origin, which might aid in distinguishing them from metastatic carcinomas, such as of breast, colon, or lung origin. Recently, the Wilms tumor gene product (WT-1) has been shown to be expressed in ovarian surface and mesothelial epithelium. We tested the hypothesis that WT-1 would be a sensitive and specific marker of ovarian surface epithelium carcinomas. An archived series of 116 ovarian carcinomas (57 serous [43 ovarian, 14 extraovarian], 31 mucinous, 15 clear cell, 13 endometrioid), 118 breast carcinomas, 46 colonic carcinomas, and 45 nonsmall cell lung cancers were selected. A polyclonal antibody to the WT-1 gene product was applied to deparaffinized, formalin-fixed tissue sections after epitope retrieval. Fifty-two of 57 (93%) serous carcinomas of ovarian surface epithelial origin were WT-1-positive, in a nuclear pattern, with virtually all the tumor cell population positive in the majority of cases. None of the mucinous, clear cell, or endometrioid ovarian cancers were positive, and only 8 of 118 breast, 0 of 46 colonic, and 0 of 45 lung nonsmall cell carcinomas were WT-1-positive. These findings demonstrate that WT-1 is a highly sensitive and specific marker of serous carcinomas of ovarian surface epithelial origin (both ovarian and extraovarian). These results also contradict recent reports demonstrating WT-1 expression in both breast and lung carcinomas.

Adenocarcinoma, Mucinous↗
PubMed2004

Mixed carcinoid and adenocarcinoma of the appendix: report of 4 cases with immunohistochemical studies and a review of the literature.

Four cases of mixed carcinoid and adenocarcinoma of the appendix were reported. All cases presented with a dominant cecal-appendiceal tumor mass and local metastasis. Two patients had multiple peritoneal implants mimicking primary peritoneal serous adenocarcinoma or carcinomatosis. Histopathologic features of the tumors are similar, with infiltrating microglandular and cribriform patterns of tumor nests, and variable numbers of goblet cells. A literature review of "goblet cell carcinoid" that included nonlocalized cases revealed a significant percentage (>14%) of tumor-associated death, in contrast to the classic carcinoid tumor. Immunohistochemical stains were helpful to separate these tumors from carcinoid tumors and primary peritoneal serous adenocarcinoma. Mixed carcinoid and adenocarcinomas were cytokeratin (CK)-20 positive, and negative or weakly positive for chromogranin A and synaptophysin. Carcinoid tumors were CK20 negative and diffusely positive for chromogranin A and synaptophysin. Peritoneal serous adenocarcinomas were CK20 negative. These cases were clinically aggressive, and 1 patient had multiple recurrences and responded partially to chemotherapy.

Adenocarcinoma↗