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[This corrects the article DOI: 10.1186/s12935-018-0634-8.].
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BACKGROUND: No data is available on the molecular background of the extra-nodal extension (ENE) of lymph node metastasis (LN) in colorectal cancer (CRC). METHODS: A series of 22 ENE-positive CRCs was considered and three samples per case were selected (the primary CRC, an ENE-negative and an ENE-positive metastatic LN). Samples (n = 66) were analysed by immunohistochemistry for PD-L1, CD4, CD8, CD68 and CD80. Fifteen out of twenty-two cases were further profiled through a hotspot multigene mutational custom panel, including 164 hotspot regions of AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN and TP53 genes. RESULTS: A significantly higher percentage of CD4-, CD8- and CD68-positive cells was observed at the invasive front of both CRCs and in ENE in contrast with what observed at the core of both CRCs and their matched nodal metastases. ENE was also characterized by a significantly higher number of CD80-positive cells. No significant difference was observed in PD-L1 distribution among the different specimens. Fourteen out of 15 CRCs (93%) showed at least a driver mutation. The most frequently mutated gene was TP53 (n = 8 tumors), followed by APC (n = 6), BRAF (n = 4), KRAS, NRAS and PIK3CA (n = 2). In 11 out of 15 CRCs (73%) the mutational profiling of the primary tumor was consistent with what obtained from the two matched LNs. CONCLUSIONS: A heterogeneous intratumor immune-microenvironment has been observed in ENE-positive CRCs, which are characterized by an increased leukocytic infiltration at the ENE invasive front.
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Squamous Cell Carcinoma Antigen (SCCA) is consistently overexpressed in many different solid tumors, and has been associated with both tumor aggressiveness and chemoresistance. No data, however, is currently available on SCCA expression during esophageal Barrett's carcinogenesis, nor on SCCA expression's role on esophageal adenocarcinoma chemoresistance. The SCCA immunohistochemical expression was assessed in a series of 100 biopsy samples covering the whole histological spectrum of Barrett's oncogenesis. Squamous native mucosa was characterized by a moderate to strong cytoplasmic and nuclear SCCA expression in suprabasal, medium, and superficial layers. On the other hand, almost half of the considered lesions did not express SCCA; the other half featured weak to moderate SCCA expression. The relationship between SCCA protein expression and tumor response to neoadjuvant chemotherapy was assessed in 90 esophageal adenocarcinoma specimens (40 biopsy and 50 surgery specimens), stratified according to Mandard tumor regression grade. As observed in other settings, the presence of SCCA expression clustered in the group of tumors characterized by a lower responsiveness to neoadjuvant treatments. The present results suggest an involvement of SCCA in a subset of Barrett-related tumors, and prompt to consider the SCCA-protein expression as response-predictive marker of neoadjuvant therapy in esophageal adenocarcinomas.