摘要:

A workshop was sponsored by the National Institute of Standards and Technology, the Cancer Diagnosis Program of the National Cancer Institute, the Food and Drug Administration, and the College of American Pathologists to address the need for a reference material for Her2 gene protein testing. It was agreed that such a standard was desirable and necessary to ensure the reliability of Her2 testing to qualify patients for trastuzumab therapy. Two standards consisting of well characterized cell lines will be produced, 1 that will be a National Institute of Standards and Technology-certifiable standard, and 1 that will be a commercially developed standard for use in all Her2 testing. It was also agreed that all Her2 testing must be performed on samples fixed only in 10% buffered formalin, as specified in the Food and Drug Administration-approved testing methods. Participants agreed to plan strategies to educate pathologists, clinicians, and laboratories about the need and use of such a standard. A National Committee for Clinical Laboratory Standards guideline for the use of the standard reference material will be created to facilitate this process.

ISSN:1541-2016    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

A variety of primary and metastatic neoplasms can involve the anterior mediastinum and have similar radiographic or histologic appearances. We report an immunohistochemical (IHC) panel that includes CD5, placental-like alkaline phosphatase (PLAP), thyroid transcription factor 1 (TTF-1), cytokeratin (CK) 7, CK20, CK5/6, and CD57 for the separation of thymic neoplasms from germ cell tumors (GCTs) and metastatic lung malignancies. One hundred cases representing different types of neoplasms involving the anterior mediastinum were retrieved and consisted of 20 pulmonary adenocarcinomas (PAs), 20 pulmonary large cell carcinomas (PLCs), 20 pulmonary squamous cell carcinomas (PSCCs), 20 thymomas (Ths), 10 invasive thymomas (IThs), and 10 thymic carcinomas (TCs). Fifteen cases of GCTs were also included in the study. CD5 was positive in 17 of 20 PAs, 11 of 20 PLCs, 2 of 15 GCTs, and 9 of 10 TCs. PLAP was positive in 5 of 20 PAs, 2 of 20 PLCs, 1 of 20 PSCCs, and 11 of 15 GCTs. TTF-1 was positive in 18 of 20 PAs, 10 of 20 PLCs, and 2 of 20 PSCCs. CK7 was positive in 20 of 20 PAs, 15 of 20 PLCs, 8 of 20 PSCCs, 5 of 15 GCTs, 11 of 20 Ths, 7 of 10 IThs, and 4 of 10 TCs. CK20 was positive only in 2 of 20 PAs. CK5/6 was positive in all cases of PSCC, Th, ITh, and TC, in 9 of 20 PLCs, and 1 of 15 GCTs. CD57 was positive in 9 of 20 PAs, 3 of 20 PLCs, 8 of 15 GCTs, 13 of 20 Ths, and 6 of 10 IThs. In conclusion, CD5 had low specificity for TC (60%) because it also stained 85% of PA and 55% of PLC. CK5/6 was a sensitive but not a specific IHC marker for the epithelial component of thymic neoplasms (100%); TTF-1 had a good sensitivity (90%) and excellent specificity (100%) for distinguishing PA from thymic neoplasms. An IHC panel consisting of CD5, CK5/6, PLAP, TTF-1, and CD57 is useful for the separation of thymic neoplasms from other epithelial malignancies involving the mediastinum.

ISSN:1541-2016    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Renal cell carcinoma antigen is a rather specific marker for normal and neoplastic renal tissue. We investigated the expression of this antigen in 34 gonadal and extragonadal germ cell tumors, including 8 pure yolk sac carcinomas and 26 embryonal carcinomas, 15 of which were combined with teratomas, seminomas, and dysgerminomas. Renal cell carcinoma antigen was demonstrated in all 8 yolk sac tumors and 21 of 26 embryonal carcinomas (81%). In yolk sac tumors, renal cell carcinoma antigen reactivity was diffusely present throughout the tumors. In embryonal carcinomas, this marker was identified only in yolk sac components. Both intracytoplasmic and membranous staining patterns were present. No reactivity was noticed in embryonal carcinoma cells, seminoma, dysgerminoma, and other components of teratomas. The study suggests an antigenic similarity between renal tubules and yolk sac tumors. Furthermore, the renal cell carcinoma antigen may be used as an addition to the panel of immunocytochemical markers for yolk sac carcinomas.

ISSN:1541-2016    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Renal cell carcinoma (RCC) not uncommonly presents with metastases and causes diagnostic difficulty to the cytopathologist who is involved in the initial diagnostic workup of tumors with an unknown primary site. RCC marker (RCC Ma) recognizes a human proximal tubule antigen and was shown to have high specificity and relatively low sensitivity in preliminary studies on routinely processed tissue sections. We investigated the diagnostic usefulness of RCC Ma immunohistochemically in fine-needle aspiration (FNA) samples. A total of 34 FNA samples obtained from the following carcinomas were used: 7 RCCs, 5 metastatic RCCs, 4 hepatocellular carcinomas, 2 non–small cell carcinomas of the lung, 3 metastatic non–small cell carcinomas of the lung, 4 invasive ductal carcinomas of the breast, 2 pancreatic ductal adenocarcinomas, 4 metastatic transitional cell carcinomas of the urinary bladder, and 3 metastatic colon carcinomas. Routinely processed cell block sections of FNA specimens were stained with RCC Ma by using routine immunohistochemistry. Presence and distribution of staining were evaluated. Two of 7 (29%) primary and 2 of 5 (40%) metastatic RCCs showed immunoreactivity in less than 50% of carcinoma cells. Staining was focal, cytoplasmic, and granular. Scattered positive cells were present in two of the four hepatocellular carcinomas. All breast, lung, pancreas, colon, and transitional cell carcinomas were negative. RCC antibody has a low sensitivity (33%), most likely because of its focal staining pattern, and a high specificity (91%) in FNA specimens. Immunoreactivity in metastatic carcinoma of an unknown primary site, especially as part of a panel of antibodies, is useful in diagnostic cytopathology. RCC antibody has not been studied in hepatocellular carcinoma, and the significance of positivity observed in some of our cases is unclear.

ISSN:1541-2016    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

HER-2/Neu overexpression is seen in 20% to 30% of invasive breast carcinomas and has been reported in as many as 80% of high-grade infiltrating carcinomas. Earlier studies have suggested that 100% of the tumor cells in mammary Paget disease show overexpression of HER-2 protein. We undertook this study to assess HER-2 status of mammary Paget disease and of the underlying breast carcinoma, when present, by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Formalin-fixed, paraffin-embedded tissue from 20 cases of mammary Paget disease were analyzed for HER-2 status by IHC and FISH. IHC for estrogen receptor (ER) was also performed. The patients ranged in age from 34 to 88 years, with a mean age of 62 years. Eighty percent of the cases showed strong overexpression (3+) of HER-2 protein by IHC, and all of these cases showed more than 5-fold amplification of the HER-2 gene by FISH. The remaining 4 cases, which were negative for HER-2/Neu by IHC, showed no amplification by FISH. All of the latter cases expressed ER, whereas no case that overexpressed HER-2 expressed ER. Sixteen cases had an underlying tumor, which was in situ in 6 cases. The underlying tumors were identical to the Paget disease with respect to their HER-2/Neu overexpression by both IHC and FISH. HER-2 overexpression was identified in 80% of our cases of Paget disease. There was 100% concordance between HER-2 protein overexpression by immunohistochemistry and gene amplification in both the Paget and the underlying tumor. Moreover, all of the cases negative for HER-2 overexpression expressed ER, whereas those positive for HER-2 did not.

ISSN:1541-2016    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

A subset of breast carcinomas shows unexplained overexpression of HER-2/neu protein without HER-2/neugene amplification. These tumors are often scored 2+ by immunohistochemistry (DAKO HercepTest). In vitro, Zonula occludens-1 (ZO-1), a tight junction protein, can upregulate HER-2/neu expression by sequestering a repressor of the HER-2/neugene promoter. To assess this relation in vivo, we examined the expression of ZO-1 in 2 series of breast carcinomas. In group 1, 35 invasive breast carcinomas previously scored by HercepTest for HER-2/neu status (negative [n = 12], 2+ [n = 13], 3+ [n = 10]) were examined by immunohistochemistry for expression of ZO-1. ZO-1 expression was then correlated with HER-2/neu expression status. Twenty-four of 35 carcinomas (69%) were positive for ZO-1 expression. Frequency of ZO-1 expression did not differ between HER-2/neu–negative carcinomas (67%) and 2+ positive carcinomas (77%). Carcinomas with 3+ HER-2/neu expression were less commonly positive for ZO-1 (60%), but this difference was not significant. Twenty tumors contained ductal carcinoma in situ (DCIS); 18 of 20 DCIS (90%) were positive for ZO-1. Interestingly, in those tumors with ZO-1–positive DCIS, 4 of 18 (22%) were negative for ZO-1 expression in the invasive tumor. In group 2, 31 of 42 (74%) fluorescent in situ hybridization-nonamplified breast carcinomas showed ZO-1 expression, also with no significant difference in frequency between HER-2/neu–positive (by immunohistochemistry) and negative cases. ZO-1 expression does not correlate with HER-2/neu expression in breast carcinomas. Other causes of HER-2/neu protein overexpression should be sought in cases without HER-2/neugene amplification.

ISSN:1541-2016    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Multiple studies using primary tumors have reported that alterations in p53 expression and detection of TP53 mutations are associated with clinical aggressiveness and poor response to specific therapies. However, there is no general agreement regarding the optimal technical approach to the analysis of p53. We have studied a series of 100 primary colorectal adenocarcinomas by immunohistochemistry with the monoclonal antibody PAb1801, and single-stranded conformation polymorphism (PCR-SSCP, exons 4–8) followed by direct sequencing of shifted bands. p53 Nuclear staining was undetectable (score 0) in 29 of 100 cases. However, gene mutations were detected in 15 of these cases, with all of these mutations leading to abnormal proteins. p53 Nuclear staining was detectable and scored as less than 10% tumor cells positive in 15 of 100 cases but was still considered to be displaying a p53-negative phenotype because the cut-off value for positivity was 10% positive tumor cells. Nevertheless, TP53 gene mutations were detected in 2 of these cases. p53 Nuclear immunoreactivities were detectable and scored as more than 10% tumor cells positive in 56 cases, considered the p53-positive phenotype. TP53 gene mutations were identified in 51 of these 56 cases. These results reveal that immunohistochemical assessment does not predict TP53 mutation status in colorectal adenocarcinoma, mainly in cases displaying absence of nuclear staining. It is thus concluded that molecular profiling should be conducted in parallel with immunophenotyping when analyzing colorectal tumors for p53 status.

ISSN:1541-2016    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The cyclins are key regulators of cell cycle progression and cellular proliferation. We have previously shown that in testicular germ cell tumors, cyclin E expression correlates with more aggressive tumors, higher clinical stage, and the presence of pulmonary metastases. Here, we have examined the association between cyclin activation and the proliferative rate of the pluripotential testicular tumor cell. We have shown that in a panel of 30 testicular germ cell tumors, 15 cases (50%) expressed the cyclin dependent kinase inhibitor p27; of note, 13 of 14 embryonal carcinomas (93%) coexpressed cyclin E and p27, suggesting inhibition of this cyclin. We show that 25 of 30 (83%) of the testicular germ cell tumors express cyclin D2. Using immunoprecipitation assays from the embryonal carcinoma cell line NTera2 or from tumor cell extracts, we have shown that cyclin D2 is complexed with p27, consistent with its known ability to sequester and block the cyclin E inhibitory function of p27. From these results, we propose a model in testicular germ cell tumors, in particular embryonal carcinomas, whereby the overexpression of cyclin D2, a gene localized on chromosome 12p–-a region of DNA amplification in germ cell tumors–-leads to the functional sequestration of p27 in the presence of cyclin E andcyclin D2,thus favoring cellular proliferation.

ISSN:1541-2016    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The presence of p24 protein was studied in lymph nodes from human immunodeficiency virus (HIV)-positive patients affected by persistent generalized lymphadenopathy. Paraffin-embedded lymph node sections from 50 HIV-1 subtype E-infected lymph nodes from patients in Thailand and 25 HIV-1 presumably subtype B-infected lymph nodes from patients in the United States were immunostained with p24 HIV major core and capsid monoclonal antibodies using the streptavidin-biotin immunoperoxidase technique. Positivity for HIV p24 protein was detected in 20 of 22 HIV-1 subtype B infected nodes in which lymphoid follicles were present, with p24 staining demonstrating a reticular pattern within the germinal centers. Interestingly, no case from 50 clade E-infected lymph nodes containing lymphoid follicles had such a reticular pattern in the germinal centers. This difference could be explained by differential infection of subsets of dendritic cells by the two HIV-1 clades, or perhaps by different routes of initial HIV-1 transmission.

ISSN:1541-2016    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Lymphoepithelioma-like carcinoma (LELC) of the stomach is reported to be associated with Epstein-Barr virus (EBV) and to have a better prognosis than typical adenocarcinoma. However, the incidence of EBV and its association withHelicobacter pyloriis controversial. In our series, 9 of 370 (2.4%) cases of gastric adenocarcinoma were LELC. Formalin-fixed, paraffin-embedded LELC tissue was immunostained with monoclonal antibodies against CD3, CD20, and Ki-67. Warthin–Starry stain forH. pyloriand in situ hybridization for EBV were performed. As a control, 21 cases of adenocarcinoma with prominent lymphoid stroma were compared with LELC. The most common location of LELC was the body of the stomach (five cases), followed by the cardia (two cases), whereas the antrum was the most common site for the control group. There were no significant differences in age, sex, or lymph node metastasis between the LELC and control groups. The mean Ki-67 index was similar (38.2% in LELC versus 35.3% in control).H. pyloriwas found in 2 LELC cases (22%) and 6 controls (28.5%). EBV was positive in 7 LELC cases (77.8%) and 4 controls (19.0%). All patients with LELC are alive and well, whereas three patients have died of their disease in the control group. Although EBV appeared to be a contributing factor,H. pylorihad a minor role in LELC. There were no clinicopathologic differences between LELC and the control group, except for the location of the tumor in the body of the stomach and the tendency toward a better prognosis in LELC.

ISSN:1541-2016    

出版商:OVID    

年代:2003

数据来源: OVID