CAMTA1 immunostaining is not useful in differentiating epithelioid hemangioendothelioma from its potential mimickers

Our plain-English summary of CAMTA1 immunostaining is not useful in differentiating epithelioid hemangioendothelioma from its potential mimickers, by Z. Yusıflı, K. Kösemehmetoğlu (Türk Patoloji Dergisi, 2014).

The study

• Authors: Z. Yusıflı, K. Kösemehmetoğlu
• Journal: Türk Patoloji Dergisi
• Published: 2014;30(3):159-65
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: Epithelioid hemangioendothelioma is a rare member of vascular tumors of intermediate malignancy. Recently, presence of t(1;3) translocation and WWTR1/CAMTA1 gene fusion, which enhances CAMTA1 expression, are found to be specific to this tumor. We investigated the CAMTA1 immune expression profile of epithelioid hemangioendothelioma and its potential mimickers using a commercially available CAMTA1 antibody.

Material And Method: Standard whole sections from the formalin fixed, paraffin embedded blocks of 12 epithelioid hemangioendotheliomas, 10 angiosarcomas, 9 epithelioid sarcomas, 8 malignant melanomas, 8 signet ring carcinomas, 7 lobular carcinomas of breast, 2 epithelioid mesotheliomas, 2 rhabdoid tumors and 12 miscellaneous hemangiomas were immunostained for anti-CAMTA1 (ab64119, 1:200; Abcam) after pretreatment with citrate pH 6.0 for 20 minutes using Leica Bond detection kit with DAB chromogen. Strong nuclear CAMTA1 expression was scored for its extent as 'negative' ( < 5% positive), '+1' (5-25% positive), '2+' (25-50% positive) and '3+' ( > 50% positive).

Results: In 60 out of 70 cases (86%) either 2+ or 3+ strong nuclear staining was seen. Eighty-three % of epithelioid hemangioendotheliomas, 100% of angiosarcomas, 89% of epithelioid sarcomas, 89% of malignant melanomas, 63% of signet ring carcinomas, 71% of lobular carcinomas of breast, 100% of epithelioid mesotheliomas, 50% of rhabdoid tumors and 100% of hemangiomas were stained. Besides neurons, CAMTA1 expression was also observed in squamous epithelium, skin adnexa, breast lobules, prostate glands, bile ducts, colonic mucosa and gastric pits.

Conclusion: Epithelioid hemangioendothelioma, its potential morphological mimickers and other benign or malignant vascular tumors showed strong and diffuse CAMTA1 expression, nullifying the potential use of CAMTA1 immunohistochemistry as an adjunct in the differential diagnosis.

In plain English

This laboratory study came from the Department of Pathology at Hacettepe University in Ankara, Turkey. It tested whether a commercially available stain for the protein CAMTA1 could help pathologists tell epithelioid hemangioendothelioma, a rare blood-vessel tumor, apart from tumors that look similar under the microscope. The authors stained 70 archived tumor samples: 12 epithelioid hemangioendotheliomas and 58 look-alike tumors, including 2 epithelioid mesotheliomas. The study did not examine asbestos or any other exposure. A tumor counted as positive when at least 25% of its cells showed moderate to strong staining in the cell nucleus. Overall, 60 of 70 tumors (86%) were positive. These included 10 of 12 epithelioid hemangioendotheliomas (83%), all 10 angiosarcomas, all 12 hemangiomas and both epithelioid mesotheliomas, as well as most epithelioid sarcomas, melanomas, signet ring carcinomas and lobular breast carcinomas. Several normal tissues besides nerve cells also stained. The authors concluded that CAMTA1 staining is not useful for this distinction and cannot replace genetic testing by FISH. They noted that the antibody might react with other proteins.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory immunohistochemistry study of archived tumor samples, testing one commercial antibody stain
• Who was studied: 70 archived tumors from the authors' department at Hacettepe University, Ankara, Turkey: 12 epithelioid hemangioendotheliomas, 10 angiosarcomas, 9 epithelioid sarcomas, 8 malignant melanomas, 8 signet ring carcinomas, 7 lobular carcinomas of breast, 2 epithelioid mesotheliomas, 2 rhabdoid tumors and 12 miscellaneous hemangiomas. Collection dates are not given.
• Exposure: No asbestos or other exposure was studied. What was tested was a stain using a commercial polyclonal anti-CAMTA1 antibody (ab64119, Abcam, diluted 1:200). Only nuclear staining counted as positive.
• Main results:
  • Across all 70 tumors, 60 (86%) showed 2+ or 3+ moderate to strong nuclear CAMTA1 staining.
  • 10 of 12 epithelioid hemangioendotheliomas (83%) were positive.
  • All angiosarcomas (10 of 10) and all hemangiomas (12 of 12) were also positive.
  • Non-vascular look-alike tumors were also positive: 2 of 2 epithelioid mesotheliomas (100%), 8 of 9 epithelioid sarcomas (89%), 7 of 8 malignant melanomas (printed as 89%), 5 of 7 lobular carcinomas of breast (71%), 5 of 8 signet ring carcinomas (63%) and 1 of 2 extrarenal rhabdoid tumors (50%).
  • In normal tissues, staining was seen in neurons and also in squamous epithelium, skin adnexa, breast lobules, prostate glands, bile ducts, colonic mucosa and gastric pits. Hepatocytes, chorionic trophoblasts, lung, thyroid, muscle fibers and fibroblasts were negative.
• The authors' conclusion: The authors concluded that CAMTA1 immunostaining is not useful in differentiating epithelioid hemangioendothelioma from its potential mimickers, and that it cannot replace FISH testing for CAMTA1 rearrangement.
• Limitations the authors state:
  • The polyclonal antibody used may cross-react with other proteins, giving non-specific staining.
  • The study did not test the non-vascular tumors by FISH, so it remains unknown whether they carry CAMTA1 rearrangements.

Topics

Medical terms in this study, explained in our Lexicon: Epithelioid, Translocation, Sarcoma, Carcinoma, Mesothelioma, Rhabdoid, Epithelium, Immunohistochemistry.

Related studies

• Malignant pleural mesothelioma mimicking the intrapulmonary growth pattern of epithelioid hemangioendothelioma — Y. Muramatsu, K. Isobe, et al. (2014)
• Malignant vascular tumours of the pleura in "asbestos" workers and endothelial differentiation in malignant mesothelioma — R.L. Attanoos, S.K. Suvarna, et al. (2000)
• How useful is GLUT-1 in differentiating mesothelial hyperplasia and fibrosing pleuritis from epithelioid and sarcomatoid mesotheliomas? An international collaborative study — A.N. Husain, M.K. Mirza, et al. (2014)
• Epithelioid hemangioendothelioma of the pleura: clinical and radiologic features — E.J. Crotty, H.P. McAdams, et al. (2000)
• Immunostaining in lung cancer for the clinician. Commonly used markers for differentiating primary and metastatic pulmonary tumors — J.M. Carney, A.M. Kraynie, et al. (2015)
• Calretinin, thrombomodulin, CEA, and CD15: a useful combination of immunohistochemical markers for differentiating pleural epithelial mesothelioma from peripheral pulmonary adenocarcinoma — C.E. Comin, L. Novelli, et al. (2001)

Browse more research in Türk Patoloji Dergisi, or return to medical research.