c-erbB-2 oncogene product staining in gastric adenocarcinoma. An immunohistochemical study

The c-erbB-2 oncogene has been shown to be amplified in a variety of human adenocarcinomas. Antibodies to the protein product, p185, have been used for immunostaining of paraffin-embedded material, and have demonstrated that high levels of c-erbB-2 protein expression correlate with gene amplification under certain conditions. In studies by others, amplification has been demonstrated in 40 per cent of tubular type adenocarcinomas of the stomach, and an immunohistochemical study on frozen tissue has demonstrated staining in 3 out of 10 cases. Our study, using paraffin-embedded material, demonstrates staining in 19 per cent of 126 cases using a polyclonal antibody. Of the positive cases, 75 per cent were tubular or papillary type (P less than 0.025), and prominent staining was restricted to this group. Three cases showed well-defined positive areas in keeping with clonal expression of p185. No specific staining of normal or dysplastic epithelium adjacent to the carcinomas was found.     

Chordoma. An immunohistochemical study of 20 cases

Twenty chordomas from 20 patients, including 17 nonchondroid and three chondroid types, were studied with a variety of antibodies directed against cytokeratin (AE-1/3), epithelial membrane antigen, carcinoembryonic antigen, S100 protein, vimentin, alpha 1-antichymotrypsin, and lysozyme. All 17 nonchondroid chordomas stained for cytokeratin, and most (16) stained for epithelial membrane antigen. In contrast, two chondroid chordomas failed to stain for either cytokeratin or epithelial membrane antigen, while one of them did stain for both antigens. Sixteen of the 20 chordomas (80%) stained for S100 protein, including all three chondroid chordomas. Vimentin was found in six (30%), and alpha 1-antichymotrypsin in 16 chordomas (80%). Carcinoembryonic antigen and lysozyme were each found in two specimens (10%). While these findings basically agree with the immunohistochemical studies of other investigators, there are a few discrepancies. Most significant is the lack of epithelial markers in two of three chondroid chordomas located at the base of the skull. Possible reasons for the discrepancies are discussed.     

Meningiomas. An immunohistochemical study of 50 cases

Fifty formalin-fixed, paraffin-embedded meningiomas were studied with a panel of ten antibodies directed against epithelial antigens, intermediate filaments, and neuroectodermal antigens. Twenty-five (50%) of these were stained with monoclonal antibodies (MoAb) to epithelial membrane antigen (EMA), 12 (24%) with keratin antibodies, 9 (18%) for vimentin, and 4 (8%) for S100 protein. Monoclonal antibodies to Leu-7, desmin, neurofilament 200 kDa, and glial fibrillary acidic protein (GFAP) all failed to stain any of the 50 neoplasms. Overall, 34 (68%) meningiomas stained with one or more antibodies. Sixteen (32%) failed to stain at all. The dual epithelial and mesenchymal nature of meningiomas is supported in this study. Applications to diagnostic surgical pathology and histogenetic implications are discussed.     

Immunoreactivity and receptor expression of insulinlike growth factor I and insulin in human adrenal tumors. An immunohistochemical study of 94 cases.

Using immunoperoxidase methods, 94 human adrenal tumors were examined for evidence of immunoreactivity and receptor expression of insulinlike growth factor I (IGF-I) and insulin. The frequency of IGF-I in adrenocortical carcinomas was significantly higher than that in adenomas of the adrenal glands. The adrenocortical carcinomas showed strong intensity of staining for IGF-I, IGF-I receptors, and insulin receptors. A significant correlation between immunoreactivity and receptor expression of both IGF-I and insulin was found only in the adrenocortical carcinomas. The adrenocortical adenomas with Cushing's syndrome and pheochromocytomas, more than adrenocortical adenomas with Conn's syndrome, also stained strongly for insulin receptors. Thus the IGF-I and insulin probably play a role in the growth of adrenocortical carcinoma tissues, possibly through autocrine mechanisms. The expression of insulin receptors in adrenocortical adenomas in the presence of Cushing's syndrome and pheochromocytomas may be associated with functions.     

Distribution of keratin protein in normal prostate and prostatic tumors. An immunohistochemical study

Fifty cases (20 cases of benign hyperplasia, 30 cases of adenocarcinoma) of prostatic tissues were studied for expression of keratin. The basal cells were strongly and continuously positive in normal prostatic glands and in benign prostatic hyperplasia. The secretory cells and carcinoma cells were negative. The basal cells remained partially in intra-ductal carcinoma, revealing keratin positive cells in a spotty pattern. These findings may be useful in differential diagnosis between benign prostatic hyperplasia and carcinoma of the prostate.     

Secondary prostatic adenocarcinoma: a cytopathological study of 50 cases

Positive diagnosis of metastatic prostate adenocarcinoma (PAC) can be made by microscopic examination of the cytologic specimens and immunostaining for prostate-specific antigen (PSA) and prostate acid phosphatase (PAP). Immunohistochemical markers have been known to display negative, weak, or focal staining in poorly differentiated PAC and in patients with prior hormonal and/or radiation therapy. The purpose of this study is to characterize the cytopathology of metastatic PAC as it has not been documented in large series. Fifty cases of metastatic PAC with cytological specimens consisting of 41 fine-needle aspiration biopsies (FNAB), 6 pleural fluid aspirates, and 3 catheterized urine samples were reviewed and correlated with the surgical specimens and the clinical charts. Immunostaining for PSA, PAP, cytokeratin AE1/3, cytokeratin 7 (CK7), cytokeratin 20 (CK20), vimentin, and carcinoembryonic antigen (CEA) was done. Mean patient age was 77 +/- 8 yr; serum PSA, 4.1 +/- 2.3; and primary PAC Gleason score, 8.1 +/- 1.5. Cytologically, the specimens consisted of cell clusters or cell sheets with overlapping uniform hyperchromatic nuclei with or without nucleoli. Twelve cases were not reactive to PSA and PAP and 44 cases displayed negative immunoreactivity to both CK7 and CK20. Carcinoid-like lesions and small cell carcinomas were seen in 4 cases and were misdiagnosed as nonprostatic origin based on the following features: negative immunoreactivity to PSA and PAP with or without positive reactivity to CEA, and different histopathological features when compared with the primary PAC. In addition to the frequency of high-grade PAC, awareness of the negative immunoreactivity to PSA and PAP, the discrepancy in the histopathological patterns between the primary and secondary tumors, especially the frequent neuroendocrine differentiation, are helpful features for the diagnosis of metastases of prostatic origin.     

Extramedullary non-gastrointestinal plasmocytoma. An immunohistochemical study of sixteen cases

Sixteen cases of extramedullary non-gastrointestinal plasmocytoma were studied for intracytoplasmic immunoglobulins by means of the immunoperoxidase-complex technique. Of the sixteen cases IgG class were observed in 4, IgM in one and IgA in 9 cases. Kappa light chains were found in 9 cases and lambda light chains in 6 cases. In one case a bitypic pattern of k- and lambda-positivity was encountered. In 2 cases only kappa light and no heavy chains were detected. The predominance of the IgA class in extramedullary, non-gastrointestinal plasmocytomas is in contrast to the prevalence of IgG type in multiple myeloma. The better possible behaviour of IgA-plasmocytomas is discussed further.     

Expression of cytokeratin and erbB-2 oncoprotein in Paget's disease of the nipple. An immunohistochemical study.

The occurrence of epithelial membrane antigen (EMA), low molecular weight cytokeratin (CK) and erbB-2 oncoprotein was investigated in twenty-eight cases of Paget's disease of the nipple (PD) to determine their diagnostic usefulness. The ABC technique with monoclonal antibodies was used on formalin-fixed, paraffin-embedded tissue. The Paget's cells showed positive immunoreactivity for all three antigens investigated in a high percentage of PD. Immunoreactivity for CK and erbB-2 oncoprotein was restricted to the Paget's cells, whereas EMA in some cases also stained the adjacent keratinocytes. Since CK and/or erbB-2 oncoprotein occurred in 93% of the cases, we conclude that demonstration of both antigens is useful in the diagnosis of PD. ErbB-2 oncoprotein was also found to be expressed in a high percentage of the underlying intraductal and invasive carcinomas.     

前列腺特殊类型癌27例临床病理与免疫组化分析

目的：探讨前列腺特殊类型癌（ＰＰＴＣ）病理变化、免疫组化表达特点。方法：采用ＨＥ及免疫组化方法观察２７例ＰＰＴＣ形态学特征。结果：（１０移行细胞癌及鳞癌具有典型的形态。癌细胞无ＰＳＡ及３５βＨ１１表达,ｃ－ｅｒｂＢ－２显阳性。从形态分析,这两种癌可能同源于移行上皮或化生上皮;（２）Ｏ产癌、导管癌、髓样癌、宫内膜样癌、乳头状癌及印戒细胞癌均显ＰＳＡ及３５βＨ１１阳性提示中癌可能来源的于分泌上皮;（３     

Collision metastasis of prostatic and colonic adenocarcinoma: report of 2 cases

Collision metastases of carcinomas in lymph nodes are rare. Carcinoma metastasizing to lymph nodes containing malignant lymphoma has also been reported. The literature contains 3 cases of collision metastasis of prostatic and urothelial carcinoma. To our knowledge, we report the first 2 cases of collision metastasis of prostatic and colonic adenocarcinoma, one involving a mesenteric lymph node and the other involving a perirectal lymph node, both from resections for colonic adenocarcinoma in patients with known metastatic prostatic carcinoma.     

Oncocytoma-like angiomyolipoma. A clinicopathologic and immunohistochemical study of 2 cases

We report the clinical, pathologic, and immunohistochemical features of an unusual tumor of the kidney composed of densely eosinophilic, polygonal epithelioid cells. The patients were a 56-year-old woman and a 35-year-old man. The renal tumors were discovered during follow-up for breast carcinoma and evaluation for abdominal pain, respectively. The tumors closely resembled oncocytoma in routine sections, but were negative for epithelial markers and positive for HMB-45, a pattern of reactions characteristic of angiomyolipoma. In the woman, a single additional microscopic angiomyolipoma was present in the renal parenchyma at a distance from the main tumor. Both patients are alive without recurrence 7 and 10 years after surgery, respectively. Based on clinical, morphologic, and immunophenotypic features, we conclude that these tumors are oncocytoma-like angiomyolipomas.     

Expression of T/NK-cell and plasma cell antigens in nonhematopoietic epithelioid neoplasms. An immunohistochemical study of 447 cases

We studied the expression of CD2, CD3, CD4, CD5, CD7, CD8, CD56, and CD138 in 447 cases of common human neoplasms with epithelioid features. CD2, CD3, CD4, and CD8 antigens were detected in none of 447 cases of nonhematopoietic tumors. CD5 and CD7 antigens were expressed in 12.3% and 19.5% of cases of nonhematopoietic tumors, respectively. Their expression was found primarily in adenocarcinomas from the gastrointestinal tract, breast, and female reproductive organs. The high expression of CD5 and CD7 antigen in pancreatic ductal carcinoma and cholangiocarcinoma and high expression of CD7 in epithelioid sarcoma may have diagnostic value. One quarter of cases were positive for CD56. Overexpression of CD56 antigen was detected mainly in neuroendocrine tumors or adenocarcinomas with neuroendocrine differentiation. Its consistent overexpression in adrenal cortical and thyroid tumors may have diagnostic usefulness. Virtually all tumor types studied were CD138+ with a variable positivity rate. The negative staining of CD138 in malignant mesothelioma may be useful for separating mesothelioma from metastatic adenocarcinoma.     

Nonspecificity of colon-specific antigen in adenocarcinomas. An immunohistochemical study of 422 cases.

To determine the specificity of colon-specific antigen in adenocarcinomas, routinely prepared paraffin-embedded tissue from 422 cases of adenocarcinoma were studied using a commercially available monoclonal antibody to colon-specific antigen and a standard avidin-biotin immunohistochemical technique. Positive reactivity for colon-specific antigen was very common (80% to 100%) in adenocarcinomas of the colon, distal esophagus/stomach, ovary, endocervix, endometrium, lung, pancreas, prostate, and bile ducts. Positive reactions were infrequent in adenocarcinomas of the breast (16%) and in hepatocellular carcinomas (23%). No immunoreactivity was seen in adenocarcinomas of the thyroid or in renal cell carcinomas. It is concluded that colon-specific antigen is not a colon-specific marker in adenocarcinomas. However, it may be useful in ruling out adenocarcinomas of renal or thyroid origin in certain clinical settings.     

Distribution of CA 125 in adenocarcinomas. An immunohistochemical study of 481 cases.

To determine the distribution of CA 125 in adenocarcinomas, formalin-fixed, paraffin-embedded tissue from 481 cases of adenocarcinoma from a variety of primary sites were studied using a monoclonal antibody to CA 125 (B27.1) and an avidin-biotin immunohistochemical technique. Positive reactivity was most common in adenocarcinomas of the endocervix, ovary, and endometrium (61% to 94%). However, relatively frequent positive reactions also were seen in adenocarcinomas of the pancreas (48%) and bile ducts (56%). Adenocarcinomas of the breast, lung, thyroid, distal esophagus/stomach, and liver (hepatocellular carcinoma) showed positive reactions in 7% to 20% of cases. Staining of rare tumor cells was seen in 2 of 45 colonic adenocarcinomas and in 1 of 61 prostatic adenocarcinomas. No reactivity was seen in the 54 renal cell carcinomas studied. Although CA 125 is most commonly present in gynecologic adenocarcinomas, it is also produced by some adenocarcinomas from many other sites. Immunostaining for CA 125 may be helpful in ruling out renal cell carcinoma in certain clinical settings.     

Comparative study of immunohistochemical expression of ERG and MAGI2 in prostatic carcinoma

Diagnosis of Prostatic adenocarcinoma (PAC) is still a problematic issue. The objective of this study was to evaluate the diagnostic and prognostic value of ERG immunohistochemical (IHC) expression compared to MAGI2.Materials and methodsThis study was conducted on 56 cases of PAC and 29 cases of nodular prostatic hyperplasia (NPH). IHC staining for ERG and MAGI2 was applied to archival formalin-fixed paraffin-embedded blocks. Semi-quantitative scoring was compared and correlated with clinicopathologic parameters and the Ki-67 index.ResultsRevealed positive ERG in 51.8% of PAC while all NPH cases were negative. On the other hand, MAGI2 was detected in 91.1% of PAC versus 17.2% of NPH. Using ROC curve, the ERG showed 53.6% sensitivity, 100% specificity, 76.5% diagnostic accuracy (DA) and area under the ROC curve 0.768 in comparison to MAGI2 that showed (91.1%, 86.2%, 88.25% and 0.948 respectively). Analysis of the combined use of the two markers revealed 95% sensitivity, 100% specificity, and 94% DA when tested synchronously. Moreover, a statistically significant inverse relationship could be detected between ERG expression and the Gleason grading group (P = 0.01) and Ki-67 index (P < 0.001). In addition, high-grade prostatic intraepithelial neoplasia (HGPIN) adjacent to carcinoma; showed positive expressions in (1/11 cases, 9.11%) for ERG and (6/11 cases, 54%) for MAGI2.ConclusionThis study recommends using both ERG and MAGI2 in a cocktail for better diagnostic validity of PAC. Only ERG expression could be a good prognostic indicator.     

Alpha-fetoprotein localization in pure ovarian teratoma. An immunohistochemical study of 12 cases

Twelve cases of pure ovarian teratoma were studied by immunohistochemical methods to determine the incidence and localization of alpha-fetoprotein (AFP) production. There were six mature teratomas (grade 0) and six immature ones (grades 1-3). Three tumors (grades 1, 3, and 3 and stages III, I, and III, respectively) had isolated foci of AFP immunoreactivity in yolk-sac-like vesicles, intestinal-type epithelium, or tissue resembling liver, whereas the other nine tumors had no AFP-positive components. The former three patients had preoperative serum AFP determinations; the values were elevated in two of them, and in both instances the oncofetoantigen became undetectable one month after oophorectomy. Both patients are alive and well 15 and 25 months later; the third patient with a normal serum AFP before surgery and a positively stained tumor died of recurrent disease. The authors' findings indicate that the production of AFP in pure ovarian teratomas recapitulates its pattern of synthesis during ontogeny. Furthermore, it is suggested that a preoperative elevation of serum AFP in a pure ovarian teratoma does not seem to correlate with stage or grade, beyond minimizing the possibility that the tumor is grade 0, or mature.     

Expression of caveolin-1 and caveolin-2 in the human pituitary: An immunohistochemical study

Caveolins are coat proteins of caveolae, the plasmalemmal transport vesicles. To our knowledge their presence in the human pituitary and various types of hypophysial adenomas has not been investigated. In the present work, expression of caveolin-1 and caveolin-2 was studied by immunohistochemistry using the streptavidin-biotin-peroxidase complex method. The material included 7 autopsy obtained, 5 surgically removed non-tumorous pituitaries, and 97 hypophysical adenomas classified on the basis of histologic immunohistochemical and ultrastructural features. No immunoreactivity was seen for caveolin-1 and caveolin-2 in non-tumorous adenohypophysial and neurohypophysial cells and in the tumor cells, indicating that caveolins are not involved in the initiation and progression of pituitary adenomas. The expression of caveolin-1 and caveolin-2 in the endothelial cells did not depend on age, gender, endocrine status of the patients, morphologic features, and type of pituitary tumors. Scattered endothelial cells were immunopositive for both caveolins showing similar cytoplasmic localization. Evidence that the two caveolins were indeed localized to the same endothelial cell was demonstrated on consecutive sections using Factor-8 and CD-34, two reliable endothelial cell markers. Not every endothelial cell was immunoreactive for the two caveolins, suggesting that the functional status of endothelial cells is not the same within the adenomas, not even in the same capillary.