The therapeutic management of patients with endoscopic resection of colorectal cancer invading the submucosa (i.e. pT1 CRC) depends on the balance between the risk of cancer relapse and the risk of surgery-related morbidity and mortality. The aim of our study was to report on the histopathological risk factors predicting lymph node metastases and recurrences in an exhaustive case series comprising every pT1 CRC (of adenocarcinoma subtype only) diagnosed in Finistère (France) during 5-years. For 312 patients with at least 46 months follow-up included in the digestive cancers registry database, histopathological factors required for risk stratification in pT1 CRC were reviewed. Patients were treated by endoscopic resection only (51 cases), surgery only (138 cases), endoscopic resection followed by surgery (102 cases) or transanal resection (21 cases). Lymph node metastases were diagnosed in 19 patients whereas 15 patients had an extra-nodal recurrence (7 local recurrences only, 4 distant metastases only and 4 combining local and distant recurrences). Four patients with distant metastases died of their cancer. Poor tumor differentiation, vascular invasion and high grade tumor budding on HES slides were notably identified as strong risk-factors of lymph node metastases but the prediction of extra-nodal recurrences (local, distant and sometimes fatal) was less obvious, albeit it was more frequent in patients treated by transanal resection than with other treatment strategies. Beyond good performances in predicting lymph node metastases and guiding therapeutic decision in patients with pT1 CRC, our study points that extra-nodal recurrence of cancer is more difficult to predict and requires further investigations.

Anti‐TRK targeted therapies offer opportunities to treat patients with advanced NTRK1/2/3‐rearranged cancers. Beyond NTRK‐rearranged secretory breast carcinomas, little is known about NTRK rearrangements and the expression of TRK proteins in non‐secretory breast carcinomas. We search for TRK proteins expressions using pan‐TRK immunohistochemistry and NTRK1, NTRK2 and NTRK3 rearrangements using fluorescent in situ hybridization (FISH) tests in a set of tissue microarray included breast carcinomas. Only 1/339 invasive breast carcinomas, the only example of secretory subtype, was positive using pan‐TRK immunohistochemistry and harboured a NTRK‐rearrangement (NTRK1 positive FISH test). According to our results, druggable NTRK rearrangements and related‐TRK proteins expression are not encountered in non‐secretory breast carcinomas.

AimWe aimed to study the prognostic value of KRAS, NRAS, BRAF mutations and microsatellite stable (MSS)/instable (MSI) in the field of colorectal cancer invading the submucosa (ie, pT1 colorectal cancer (CRC)).MethodsWe led a case-control study in tumour samples from 60 patients with pT1 CRC with (20 cases) and without (40 cases) metastatic evolution (5 years of follow-up) which were analysed for KRAS, NRAS, BRAF mutations (Idylla testing and next generation sequencing, NGS) and MSS/MSI status (Idylla testing and expression of mismatch repair (MMR) proteins using immunohistochemistry).ResultsKRAS mutations were encountered in 11/20 (55%) cases and 21/40 (52.5%) controls (OR=1.11 (0.38 to 3.25), p=0.8548), NRAS mutations in 1/20 (5%) cases and 3/40 (7.5%) controls (OR=3.08 (0.62 to 15.39), p=0.1698) and BRAF mutations in 3/20 (15%) cases and 6/40 (15%) controls (OR=1.00 (0.22 to 4.5), p=1.00). A MSI status was diagnosed in 3/20 (15%) cases and 5/40 (12.5%) controls (OR=1.2353 (0.26 to 5.79), p=0.7885). Beyond the absence of significant association between the metastatic evolution and any of the studied molecular parameters, we observed a very good agreement between methods analysing KRAS, NRAS and BRAF mutations (Kappa value of 0.849 (0.748 to 0.95) between Idylla and NGS) and MSS/MSI (Idylla)—proficient MMR/deficient MMR (immunohistochemistry) status (Kappa value of 1.00).ConclusionAlthough being feasible using the fully automated Idylla method as well as NGS, the molecular testing of KRAS, NRAS, BRAF and MSS/MSI status does not seem useful for prognostic purpose in the field of pT1 CRC.

No abstract

NTRK-rearranged tumors could be treated using promising anti-TRK–targeted therapies in patients with advanced cancers including melanomas. Different targeted therapies are being developed together with different screening strategies including pan-TRK immunohistochemistry (IHC) as first-line screening strategies. In this technical study, we compared 2 pan-TRK IHC (using A7H6R and EPR17341 clones) in tumor samples of patients with advanced melanomas. IHC-positive cases were studied using NTRK1, NTRK2, and NTRK3 fluorescent in situ hybridization tests. Among 300 melanoma samples, 4 samples were positive using A7H6R IHC, but none using EPR17341. None of the 4 samples were NTRK-rearranged using fluorescent in situ hybridization. Different staining was also noted in nontumor kidney tissue, whereas an NTRK1-rearranged tumor used as positive control was strongly stained with both A7H6R and EPR17341 clones. Future studies including more numerous NTRK-rearranged tumors are required to further study and compare the performances of different pan-TRK clones in the screening of NTRK-rearranged cancers.