A33 shows similar sensitivity to but is more specific than CDX2 as an immunomarker of colorectal carcinoma

Aims: CDX2 is widely used as a sensitive and specific immunomarker for colorectal carcinoma (CRC) but neither this sensitivity nor specificity is absolute. This study is the first known comparison of CDX1 and A33 against CDX2 as immunomarkers for CRC. Methods and Results: As a pilot study, whole sections of 51 cases of liver metastatic carcinoma of different origins - colorectum (n=32), breast (n=3), oesophagogastric tract (n=4), lung (n=3), pancreas (n=8), and prostate (n=1) - were immunostained with CDX1, CDX2 and A33. Compared with CDX1, A33 showed higher sensitivity as a CRC immunomarker, greater interobserver reproducibility for assessment of expression, and less background cross-reactivity. Therefore, only A33 was compared with CDX2 for a tissue microarray-based study of primary adenocarcinomas of different origin: CRC (n=55), liver deposits of metastatic CRC (n=60), breast (n=101), lung (n=40), oesophagogastric tract (n=134), ovary (n= 67), pancreas (n= 77), and prostate (n= 56). Combining the whole section and TMA cases of CRC, A33 had a sensitivity of 95.9% and CDX2 a sensitivity of 97.2%. Combining all the whole section and TMA cases of non-colorectal carcinomas, A33 showed 85.4% specificity as a marker of CRC compared to CDX2 which showed a specificity of 64.3%. The higher specificity of A33 as a colorectal carcinoma immunomarker compared with CDX2 was particularly seen amongst pancreatic and ovarian carcinomas. Further, unlike with CDX2, none of the prostatic and lung carcinomas studied showed A33 positivity. Conclusions: A33 shows similar sensitivity to but is more specific than CDX2 as an immunomarker of CRC

HER2 testing of gastro-oesophageal adenocarcinoma:a commentary and guidance document from the Association of Clinical Pathologists Molecular Pathology and Diagnostics Committee

The use of biologics targeted to the human epidermal growth factor receptor 2 (HER2) protein is the latest addition to the armamentarium used to fight advanced gastric or gastro-oesophageal junction adenocarcinoma. The decision to treat with the biologic trastuzumab is completely dependent on HER2 testing of tumour tissue. In 2017, the College of American Pathologists, American Society for Clinical Pathology and the American Society of Clinical Oncology jointly published guidelines for HER2 testing and clinical decision making in gastro-oesophageal adenocarcinoma. The Association of Clinical Pathologists Molecular Pathology and Diagnostics Committee has issued the following document as a commentary of these guidelines and, in parallel, to provide guidance on HER2 testing in National Health Service pathology departments within the UK. This guidance covers issues related to case selection, preanalytical aspects, analysis and interpretation of such HER2 testing.</jats:p