Simona Gurzu1, Annamaria Fetyko2, Tivadar Bara3, Laura Banias4, Vlad Olimpiu Butiurca3, Tivadar Bara3, Vlad Tudorache4, Ioan Jung4. 1. Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology, George Emil Palade, Tirgu-Mures, Romania; Department of Pathology, Clinical County Emergency Hospital, Tirgu-Mures, Romania; Department of Pathology, Research Center of the University of Medicine, Pharmacy, Sciences and Technology, George Emil Palade, Tirgu-Mures, Romania. Electronic address: simonagurzu@yahoo.com. 2. Department of Pathology, Clinical County Emergency Hospital, Tirgu-Mures, Romania. 3. Department of Surgery, University of Medicine, Pharmacy, Sciences and Technology, George Emil Palade, Tirgu-Mures, Romania. 4. Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology, George Emil Palade, Tirgu-Mures, Romania.
Abstract
BACKGROUND: Mixed adenoneuroendocrine carcinoma (MANEC) is currently included in the category of neuroendocrine carcinomas but the therapeutically management is not yet defined. AIMS: To present the immunohistochemical (IHC) features of the epithelial mesenchymal transition (EMT) of MANEC. MATERIALS AND METHODS: The clinicopathological features of 13 consecutive cases of MANEC (6 gastric and 7 colorectal) were correlated with the IHC expression of the biomarkers E-cadherin, β-catenin, N-cadherin, vimentin, maspin, CD44 and S100. In all of the cases open surgery was performed. RESULTS: All of the cases showed microsatellite stable status, expressed E-cadherin and membrane β-catenin in both components (neuroendocrine and adenocarcinoma) and were negative for N-cadherin, vimentin and S-100. The colorectal MANECs were negative for maspin. In gastric MANECs, maspin showed cytoplasm positivity in the neuroendocrine component and nuclear translocation in the adenocarcinoma cells. CD44 was positive in all of the cases, in both components. No tumor buddings were identified. Three of the 13 patients survived for at least 32 months, all of them showing lymphatic emboli but not lymph node metastases. Pure neuroendocrine lymph node metastases were seen in only four of the cases: one from stomach, two of the ascending colon and two cases of the upper rectum. CONCLUSIONS: Gastrointestinal MANEC is a microsatellite stable tumor with nodular growth, which components might originate from a CD44-positive stem-like precursor cell. Lymph node status remains the most reliable prognostic parameter and agressivity seems to not be influenced by tumor budding degree or EMT-related features. The histologic aspect of metastatic component (neuroendocrine versus adenocarcinoma) should be included in the histopathological reports and might be used for establishing the proper-targeted therapy of MANEC.
BACKGROUND: Mixed adenoneuroendocrine carcinoma (MANEC) is currently included in the category of neuroendocrine carcinomas but the therapeutically management is not yet defined. AIMS: To present the immunohistochemical (IHC) features of the epithelial mesenchymal transition (EMT) of MANEC. MATERIALS AND METHODS: The clinicopathological features of 13 consecutive cases of MANEC (6 gastric and 7 colorectal) were correlated with the IHC expression of the biomarkers E-cadherin, β-catenin, N-cadherin, vimentin, maspin, CD44 and S100. In all of the cases open surgery was performed. RESULTS: All of the cases showed microsatellite stable status, expressed E-cadherin and membrane β-catenin in both components (neuroendocrine and adenocarcinoma) and were negative for N-cadherin, vimentin and S-100. The colorectal MANECs were negative for maspin. In gastric MANECs, maspin showed cytoplasm positivity in the neuroendocrine component and nuclear translocation in the adenocarcinoma cells. CD44 was positive in all of the cases, in both components. No tumor buddings were identified. Three of the 13 patients survived for at least 32 months, all of them showing lymphatic emboli but not lymph node metastases. Pure neuroendocrine lymph node metastases were seen in only four of the cases: one from stomach, two of the ascending colon and two cases of the upper rectum. CONCLUSIONS: Gastrointestinal MANEC is a microsatellite stable tumor with nodular growth, which components might originate from a CD44-positive stem-like precursor cell. Lymph node status remains the most reliable prognostic parameter and agressivity seems to not be influenced by tumor budding degree or EMT-related features. The histologic aspect of metastatic component (neuroendocrine versus adenocarcinoma) should be included in the histopathological reports and might be used for establishing the proper-targeted therapy of MANEC.