Applied Immunohistochemistry & Molecular Morphology

Our medical research library holds 15 studies published in Applied Immunohistochemistry & Molecular Morphology (2002–2020). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 13 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it. For 1 study PubMed has no abstract for, we give the abstract printed in the article or, where there is none, a summary we wrote from it, each labeled as such.

About the journal

• Publisher: Lippincott Williams & Wilkins
• Published: 1999 to the present, United States
• Language: English
• ISSN: 1541-2016 (print), 1533-4058 (electronic)
• Merged from: Cell Vision
• Merged from: Applied Immunohistochemistry
• Absorbed: Diagnostic Molecular Pathology
• Its record in the NLM Catalog

2020s

• Does Simian Virus 40 (SV40) Have a Role in UK Malignant Pleural Mesothelioma? No Role is Identified in a Sensitive RNA In Situ Hybridization Study on Potentially Affected Birth Cohorts. F.S. Alchami, R.L. Attanoos, A. Gibbs, et al. 2020;28(6):444-447. PubMed · Publisher

  Abstract

  Background: Simian virus 40 (SV40)-contaminated polio vaccine was accidentally administered to about one-third of the UK population receiving polio vaccines between 1956 and 1962. SV40 was subsequently demonstrated to be a carcinogenic virus in experimental and animal models. Since then, the SV40 oncogenic protein large T antigen (SV40 Tag) has been shown to cause malignant transformation of asbestos-treated human pleural mesothelial cells and malignant pleural mesotheliomas in asbestos-exposed SV40 Tag transgenic mice. The present study was designed to investigate the possible association of SV40 Tag with human malignant pleural mesothelioma samples from birth cohorts of the UK population exposed to combined peak levels of asbestos and SV40-contaminated polio vaccines.

  Materials And Methods: Tumor and background lung tissue microarrays prepared from archival surgical specimens of 139 pleural mesothelioma cases, collected over a period of 8 years (1998 to 2005), were analyzed. These represented birth cohorts overlapping with the period 1950 to 1960, exposed to a high level of both asbestos and SV40-contaminated live polio vaccines. SV40 Tag mRNA expression was investigated using a highly sensitive and specific SV40 Tag RNA in situ hybridization detection method on the basis of the novel RNAscope technology.

  Results: SV40 Tag RNA was not detected in any of the 127 evaluable tumor cases, despite appropriate results obtained for the external positive and negative controls included.

  Conclusion: The complete absence of SV40 Tag mRNA in this large series of cases contradicts experimental evidence suggestive of SV40 link with asbestos-exposed malignant pleural mesotheliomas in the UK population. Alternative explanations of the negative findings are discussed to exclude possible confounding factors.

2010s

• Aberrant Cytokeratin 20 Reactivity in Epithelioid Malignant Mesothelioma: A Case Report. R. Manur, I. Lamzabi. 2019;27(10):e93-e96. Case report PubMed · Publisher

  Abstract

  Malignant mesothelioma is an uncommon neoplasm that should be distinguished from the more common pulmonary adenocarcinomas and other metastatic lesions. Although diagnosis is based on morphologic features, immunohistochemical stains such as Calretinin, WT-1, CK-5/6, D2-40, Ber-Ep4, and MOC-31 are routinely used. Other organ-specific immunohistochemical markers are used when metastases from unknown primary lesion is suspected clinically. Here, we report a case of pleural epithelioid malignant mesothelioma expressing CK20. A 68-year-old male presented to the Emergency Department with nonproductive cough and progressive shortness of breath. Chest x-ray showed a large left-sided pleural effusion. Metastasis from a gastrointestinal primary was clinically suspected. Cytopathologic examination of the pleural fluid demonstrated atypical cells singly and in clusters with round nuclei, prominent nucleoli, and dense cytoplasm. The cell block demonstrated single and clusters of atypical cells positive for calretinin, D2-40, WT-1, CK-5/6, and CK7. Ber-EP4, MOC-31, TTF-1, Napsin-A, and CDX-2 were negative. CK20 was diffusely positive. A diagnosis of atypical mesothelial proliferation with aberrant CK20 expression was made. A subsequent pleural biopsy demonstrated sheets of highly atypical cells that were diffusely and strongly positive for the mesothelial markers and CK20. Multiple studies have shown malignant mesotheliomas to lack CK20 reactivity. To our knowledge, this is the first case report of a diffuse and strong CK20-positive mesothelioma. Such aberrant expressions should be kept in mind when cases are histologically atypical or lack reactivity for multiple mesothelial markers, especially when a gastrointestinal primary malignancy is suspected.

• Podoplanin is Positive Not Only on Follicular Dendritic Cells and Their Tumoral Counterparts, But Also on Reticular Fibroblasts and in Some Tumors of Reticular Fibroblasts. D. Suárez-Vilela, F.M. Izquierdo. 2016;24(2):e11. Letter · Comment PubMed · Publisher

• Low frequency of EGFR mutations in pleural mesothelioma patients, Cologne, Germany. V. Schildgen, O. Pabst, R.L. Tillmann, et al. 2015;23(2):118-25. PubMed · Publisher

  Abstract

  EGFR mutations were previously found in patients suffering from peritoneal mesothelioma but have not yet been described in pleural mesothelioma. The aim of the present study was the identification of EGFR mutations in patients suffering from pleural mesothelioma. Pleural mesothelioma tissue from 31 patients was used to analyze possible mutations in the EGFR gene comprising the exons 18-21 with the codons 719, 768, 790, 858+861, 731+734, 785, 797+801, 831, and 868 with pyrosequencing. The results indicate that 31 pleural mesothelioma patients show a wild-type EGFR gene when analyzing the codons D19, 768, 790, 858+861, 731+734, 785, 797+801, 831, and 868, whereas 2 patients have a mutation in the EGFR gene in codon 719. Sanger sequencing of the EGFR codon 785 was used for the determination of a polymorphism in the sequencing of tumor-free patients and pleural mesothelioma patients with a distribution of a wild-type homozygous sequence with guanine, a wild-type heterozygous sequence having guanine and adenine, a wild-type homozygous sequence with adenine, and a wild-type heterozygous sequence with adenine and guanine. Next, the identification of less EGFR mutations in the EGFR gene of the pleural mesothelioma an up to this time unknown polymorphism in the EGFR gene was identified which could be wrongly interpreted as a mutation.

• Immunohistochemical expression of calretinin in ameloblastoma, adenomatoid odontogenic tumor, and keratocystic odontogenic tumor: a comparative study. A. Koneru, K. Hallikeri, G.S. Nellithady, et al. 2014;22(10):762-7. PubMed · Publisher

  Abstract

  Calretinin is expressed primarily in the central and peripheral nervous system and extensively studied in colon adenocarcinoma and mesotheliomas. Calretinin is known to be expressed in the odontogenic epithelium and odontogenic tumors. However, the role of calretinin in the pathogenesis of odontogenic tumors is yet to be confirmed. Hence, the aim of the present study was to evaluate the expression and role of calretinin in selected odontogenic tumors. The study included 30 ameloblastomas, 30 adenomatoid odontogenic tumors, and 30 keratocystic odontogenic tumors. Staining intensity, pattern, and localization of the immunopositive cells were determined. Statistical analysis was performed using Mann-Whitney U test and Kruskal-Wallis analysis of variance test. P-values <0.05 were considered to be statistically significant. Results showed that 90% ameloblastomas and 80% keratocystic odontogenic tumors were immunopositive to calretinin, whereas none of the adenomatoid odontogenic tumors showed reactivity. Intensity was higher in the ameloblastomas compared with the keratocystic odontogenic tumors. Statistically significant differences were observed when the expression of calretinin was compared, except between the ameloblastoma and keratocystic odontogenic tumor. However, the intensity of calretinin was significantly higher in the ameloblastoma when compared with the keratocystic odontogenic tumor. On the basis of these results, it is suggested that calretinin might be used as a specific immunohistochemical marker for the ameloblastomas and could play an important role in the differentiation of aggressiveness of different odontogenic tumors. Depending on the cell regulatory processes, we suggest a possible role of calretinin in the pathogenesis of ameloblastomas and have to be further studied along with other proliferative cell cycle and apoptotic markers with larger sample size.

• p40 is the best marker for diagnosing pulmonary squamous cell carcinoma: comparison with p63, cytokeratin 5/6, desmocollin-3, and sox2. T. Tatsumori, K. Tsuta, K. Masai, et al. 2014;22(5):377-82. PubMed · Publisher

  Abstract

  Histologic distinction among non-small cell lung carcinomas, particularly between squamous cell carcinoma (SQC) and adenocarcinoma (ADC), has become more important. Recently, a p40 antibody was suggested to be a highly specific marker for SQC. We evaluated p40 expression and compared it with the expression of other SQC markers in 580 primary lung carcinomas, including 158 SQCs, 156 ADCs, 50 carcinoid tomors, 107 large cell neuroendocrine carcinomas, 68 small cell lung carcinomas, and 41 malignant mesotheliomas. Detailed histologic distributions of p40-positive cases were as follows: 153 (96.8%) of 158 SQCs, 7 (4.6%) of 152 ADCs, 0 (0%) of 50 carcinoid tomors, 4 (3.6%) of 107 large cell neuroendocrine carcinomas, 1 (1.5%) of 68 small cell lung carcinomas, and 1 (2.4%) of 41 mesotheliomas. p40 staining yields high sensitivity as well as high specificity for distinguishing SQC from ADC, neuroendocrine carcinomas, and malignant mesothelioma.

• Value of calretinin immunostaining in diagnostic pathology: a review and update. N.G. Ordóñez. 2014;22(6):401-15. Review PubMed · Publisher

  Abstract

  Calretinin is a member of the EF-hand family of calcium-binding proteins. Because its expression is highly restricted to mesotheliomas, calretinin is, at present, the most commonly used positive mesothelioma marker that is most often recommended to be included in the various immunohistochemical panels used to assist in the differential diagnosis of these tumors. Calretinin expression has also been reported to be commonly expressed in a wide variety of other neoplasms, including sex cord-stromal tumors, adrenal cortical neoplasms, olfactory neuroblastomas, Schwann cell tumors, cardiac myxomas, and ameloblastomas. This article reviews the information that is currently available on calretinin expression in tumors and on its application as an immunohistochemical marker in diagnostic pathology.

• Value of podoplanin as an immunohistochemical marker in tumor diagnosis: a review and update. N.G. Ordóñez. 2014;22(5):331-47. PubMed · Publisher

  Abstract

  Podoplanin is a type I integral membrane glycoprotein that, because it is expressed in lymphatic endothelium, but not in vascular blood vessel endothelial cells, is commonly used in the identification of lymphatic endothelial differentiation in vascular endothelial neoplasms and lymphatic invasion by tumor. Because podoplanin is also expressed in mesothelial cells and fetal gonocytes, it has proved to be a useful marker for assisting in the differential diagnosis of mesotheliomas and germ cell tumors, particularly seminomas/dysgerminomas. Podoplanin expression has also been reported in a wide variety of other neoplasms, including hemangioblastomas, meningiomas, cartilaginous tumors, and follicular dendritic cell neoplasms. This article reviews the information that is currently available on the application of podoplanin immunostaining in diagnostic pathology.

• Melan A (A103) is not a marker of mesothelioma. N.G. Ordóñez, S.S. Shen, M. Zenali, et al. 2013;21(2):181-4. PubMed · Publisher

  Abstract

  Although a large number of immunohistochemical markers have been proven to be valuable in the differential diagnosis between epithelioid mesotheliomas and metastatic carcinomas involving the serosal membrane, no single antibody has been found that is absolutely sensitive and/or specific in making this distinction. A recent study reported melan A positivity in all 12 of the epithelioid mesotheliomas stained with a melan A antibody (clone A103). To fully determine the practical value of this antibody for assisting in the differential diagnosis of mesotheliomas, we investigated the expression of melan A (A103) in 40 mesotheliomas (27 epithelioid, 6 sarcomatoid, and 7 biphasic), 10 lung adenocarcinomas, and 10 serous carcinomas of the ovary. None of the mesotheliomas, lung adenocarcinomas, or serous carcinomas of the ovary were melan A (A103) positive. Similar staining results were observed in the 20 mesotheliomas immunostained in another institution using the same antibody clone from a different commercial source. On the basis of these results, it is concluded that in contrast to the initial report, melan A (A103) is not expressed in mesotheliomas and therefore, immunostaining with this antibody has no utility in the diagnosis of mesothelioma. The possible cause of the discrepancies between the results obtained in the present investigation and those of the initial study is discussed.

• Is PAX2 a reliable marker in differentiating diffuse malignant mesotheliomas of peritoneum from serous carcinomas of müllerian origin?. F.F. Gao, A.M. Krasinskas, M. Chivukula. 2012;20(3):272-6. PubMed · Publisher

  Abstract

  Diffuse peritoneal malignant mesotheliomas (DPMM) are often disseminated in the peritoneal cavity as multiple nodules including localized masses in the ovaries that are clinically and histologically similar to serous adenocarcinomas of müllerian origin. It is imperative to differentiate these tumors given their diverse responses to chemotherapy and/or radiotherapy. PAX2 gene was recently demonstrated in benign epithelial cells of the female genital tract and in serous carcinomas (SC) of müllerian origin. The aim of our study was to determine if PAX2 can reliably be used in differentiating DPMM from SC. A total of 59 cases to include 25 cases of DPMM and 34 cases of SC were retrieved. All cases were stained with PAX2, Wilm tumor gene 1, calretinin and the results were compared. Our results demonstrate that PAX2 can be used reliably as a Müllerian marker in formulating an efficient panel to differentiate DPMM and SC.

• The use of immunohistochemistry in the diagnosis of composite and collision tumors: exemplified by pleural mesothelioma and carcinoid tumor of the lung. N.G. Ordóñez. 2012;20(4):421-6. Case report PubMed · Publisher

  Abstract

  A case of a collision lymph node metastasis of a mesothelioma and a carcinoid tumor in a 73-year-old man with a history of asbestos exposure is reported. An interesting finding in this case was that both the mesothelioma and its lymph node metastases exhibited a wide variety of histologic patterns, including one characterized by a solid growth of large cells with abundant, clear, and foamy cytoplasm and another exhibiting deciduoid features. Pathologists should be aware that mesotheliomas can present very unusual morphologic features, such as those seen in the present case, and therefore, should be included in the differential diagnosis of those tumors that can display similar morphology and can metastasize to the serosal membranes. Reexamination of the pneumonectomy specimen in the current case identified a primary peripheral carcinoid tumor. The recognition of a nonasbestos-related tumor in a patient with mesothelioma is important since its presence may have an impact on the patient's life expectancy and, therefore, may affect any compensation settlement.

• Skin metastasis of pleural epithelioid malignant mesothelioma. T. Terada. 2011;19(1):92-3. Case report · Letter PubMed · Publisher

  Summary

  This letter to the editor described a rare case of skin metastasis from pleural epithelioid malignant mesothelioma in a 75-year-old Japanese man with a history of asbestos exposure, seen at a hospital in Shizuoka, Japan. He presented with shortness of breath and chest pain. Imaging showed right pleural effusion and mild right pleural thickening. Cytology and a needle biopsy of the pleura were interpreted as adenocarcinoma, and he was treated with anticancer drugs for lung adenocarcinoma. Eight months later, a raised, mobile skin tumor appeared on the chest wall away from the biopsy site. Skin biopsy showed malignant epithelioid cells in the dermis, arranged in solid nests with focal tubular structures, with many tumor cells inside blood vessels. On immunohistochemistry the tumor was positive for markers including calretinin, WT-1, cytokeratin 5/6, thrombomodulin and HBME-1, and negative for CEA and B72.3. A diagnosis of skin metastasis of malignant mesothelioma was made. Re-examination of the pleural biopsy showed similar findings, and the diagnosis was corrected to malignant pleural mesothelioma. He was treated with chemoradiation but died of mesothelioma 19 months after first symptoms. The author considered the spread to be blood-borne because the skin lesion was not continuous with the pleural lesion. He concluded that mesothelioma should be considered in pleural biopsies resembling adenocarcinoma, that immunohistochemistry should be done, and that mesothelioma should be suspected in almost any pleural lesion.

  PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

• Value of D2-40 in the differential diagnosis of pleural neoplasms with emphasis on its positivity in solitary fibrous tumor. Y. Hu, Q. Yang, L.A. McMahon, et al. 2010;18(5):411-3. PubMed · Publisher

  Abstract

  D2-40 is a new monoclonal antibody recognizing podoplanin and it is selective for lymphatic endothelium. Several studies have confirmed the reliability of D2-40 in the diagnosis of pleural malignant mesothelioma, but the evaluation of this antibody in other pleural neoplasms is limited. The aim of this study was to determine the diagnostic value of D2-40 in segregation of malignant mesothelioma from other pleural or lung neoplasms. Sixty-seven cases, including 36 pleural malignant mesotheliomas, 15 solitary fibrous tumors, 13 pleomorphic carcinomas, and 3 synovial sarcomas, were immunohistochemically studied using a D2-40 monoclonal antibody. Twenty-five (21 epithelioid and 4 biphasic) of 36 (69%) malignant mesotheliomas and 2 of 15 (13%) solitary fibrous tumors were positive for D2-40. The difference of D2-40 positivity between these 2 types of tumor was significant (P<0.001). No D2-40 positivity was detected in pleomorphic carcinomas (n=13) or synovial sarcomas (n=3). These findings showed that D2-40 was frequently positive in malignant mesothelioma, but could also be positive in a small portion of solitary fibrous tumor. These results indicate that D2-40 is a valuable marker for malignant mesothelioma, but caution should be taken when evaluating D2-40-positive pleural spindle cell neoplasms in limited small biopsy specimens, especially when the differential diagnosis includes solitary fibrous tumor and malignant mesothelioma.

2000s

• Cytokeratin 5/6 immunostaining in hepatobiliary and pancreatic neoplasms. D.M. Vlasoff, D.Y. Baschinsky, W.L. Frankel. 2002;10(2):147-51. PubMed · Publisher

  Abstract

  Immunohistochemistry with different cytokeratin subsets has been successfully used in the differential diagnosis of various human epithelial neoplasms. Cytokeratin 5/6 antibody, which recently became commercially available, has been found useful in the diagnosis of mesothelioma. Studies have reported only infrequent staining in adenocarcinomas. We investigated the pattern of immunoreactivity for cytokeratin 5/6 in hepatobiliary and pancreatic tumors to determine its diagnostic utility in the morphologic evaluation of these neoplasms. Formalin-fixed. paraffin-embedded tissue sections from 10 hepatocellular carcinomas, seven hepatocellular adenomas, 10 cholangiocarcinomas, 10 pancreatic ductal adenocarcinomas, and 13 pancreatic neuroendocrine carcinomas were immunostained with anticytokeratin 5/6 after heat-induced antigen retrieval utilizing a modified avidin-biotin complex technique. Positive and negative controls stained appropriately. Two pathologists evaluated the slides. Strong but focal cytoplasmic immunoreactivity was observed in five of 10 pancreatic ductal adenocarcinomas and two of 10 cholangiocarcinomas. No immunoreactivity was identified in any cases of hepatocellular carcinoma (0/10), hepatocellular adenoma (0/7), or pancreatic neuroendocrine carcinoma (0/13). Additionally, occasional cytokeratin 5/6 immunoreactive benign ductal epithelial cells were seen in the background in some cases. Fifty percent of pancreatic ductal adenocarcinomas and 20% of cholangiocarcinomas are positive with anti-cytokeratin 5/6 immunostaining. For the evaluation of poorly differentiated neoplasms in the liver, immunoreactivity with cytokeratin 5/6 may help to exclude the possibility of hepatocellular carcinoma. Cytokeratin 5/6 may be helpful as a component in the panel of immunostains to differentiate between poorly differentiated neoplasms.

• Diagnostic use of muscle markers in the cytologic evaluation of serous fluids. A.M. Afify, B.M. Al-Khafaji, A.F. Paulino, et al. 2002;10(2):178-82. PubMed · Publisher

  Abstract

  Differentiating reactive mesothelial cells from malignant mesotheliomas and from adenocarcinomas can be diagnostically challenging when based solely on the morphologic examination of serous fluids. The diagnosis even after the use of standard immunohistochemical stains may at times be inconclusive because of the variable reactivity of mesothelial cells for these markers. Pathologists and cytologists underutilize reactivity for desmin, a feature of mesothelial cells apparently not shared by adenocarcinomas. The purpose of this study was to evaluate the extent to which mesothelial cells express muscle differentiation and to assess the diagnostic utility of muscle markers in distinguishing reactive mesothelial cells from malignant mesotheliomas and adenocarcinomas. Archival paraffin-embedded cell blocks of serous fluids from 24 cases of reactive mesothelial cells, 14 cases of malignant mesothelioma, and 56 cases (14 cases from each) of metastatic adenocarcinoma from the lung, breast, ovary, and gastrointestinal tract were retrieved. Five cases of omentum with unremarkable mesothelial cells were also included in the study. All cases were stained for desmin, actin, myoglobin, and myogenin and evaluated independently by two observers. Strong cytoplasmic reactivity for desmin was noted in 22 of 24 cases (92%) of reactive mesothelial cells. The reactive mesothelial cells did not express actin, myoglobin, or myogenin. All cases of malignant mesothelioma and metastatic adenocarcinoma were negative for the four muscle markers. The mesothelial lining and scattered subserosal cells in the omental sections were positive for desmin. Because desmin was expressed only in benign mesothelial cells, it may serve as a reliable marker in distinguishing reactive mesothelial cells from mesothelioma or from adenocarcinoma. Awareness of this staining pattern is also important to avoid pitfalls when evaluating body fluid specimens from patients with a history of tumors expressing muscle differentiation.

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