HER2 Status in RAS and BRAF Wild-Type Metastatic Colorectal Cancer: A Portuguese Study.

INTRODUCTION: Colorectal cancer (CRC) is the second-most deadly cancer worldwide. However, there remains a scarcity of precision treatments available for this type of cancer. Amplification or overexpression of human epidermal growth factor receptor 2 (HER2+) is a well-established therapeutic target in gastric and breast cancer. HER2 is positive in approximately 5% of CRC cases and has been implicated in resistance to therapy with anti-epidermal growth factor receptor antibodies. The aim of this study was to evaluate HER2 status in RAS and BRAF wild-type metastatic CRC (mCRC) and its correlation with survival outcomes. MATERIALS AND METHODS: A single-center retrospective analysis of RAS and BRAF wild-type mCRC patients undergoing systemic treatment was conducted from July 2014 to September 2020. Tissue HER2 status was determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) and/or chromogenic in situ hybridization (CISH). HER2+ was defined as IHC3 (+) or IHC2 (+) through FISH or CISH (+). RESULTS: Fifty-nine patients were included. The median age of all the included patients was 64 years (33-82). Four patients had HER2+ tumors (7%). Four patients had HER2+ tumors (7%). The majority of HER2+ mCRC cases were males (n=3) and left-sided CRC (n=3). All patients received FOLFIRI plus cetuximab as first-line treatment. At the median follow-up of 24.0 months, patients with HER2-negative mCRC presented with a median overall survival (mOS) of 39.4 months (95% confidence interval (CI) 32.7-46.0) and the four patients with HER2+ mCRC had a mOS of 20.4 months (95% CI; 9.5-31.3; p=0.07). In HER2-negative patients, the median PFS (mPFS) was 11.3 months (95% CI; 9.2-13.4) vsHER2-positive patients with a mPFS of 10.9 months (95% CI; 1.3-20.4; p=0.47). CONCLUSIONS: To our knowledge, this is the first study reporting HER2+ in mCRC patients in a Portuguese population and the HER2+ rate was consistent with previous studies. Our study suggests that HER2+ may potentially be a marker that is able to predict poor prognosis in RAS and BRAF wild-type mCRC.

Duodenal lymphangiectasias - The first sign of pancreatic adenocarcinoma.

A 41-year-old caucasian female, with past medical history of pituitary adenoma medicated with cabergoline, presented with worsening dyspepsia and unintentional weight loss of 5%. Physical exam and laboratory results were unremarkable for pathological findings. Esophagogastroduodenoscopy revealed an oedematous and exuberant lymphangiectasia appearance in the duodenum, with no ulceration or suspected infiltration component. However, duodenal biopsies revealed infiltration by poorly differentiated carcinoma. In the meantime, infection and inflammatory/autoimmune causes were ruled out. A CT scan was performed revealing a thickened and enlarged pancreas with ill-defined limits and several intra-abdominal adenopathies, raising suspicion of pancreatic lymphoproliferative disease. EUS with FNB was performed with biopsy of the pancreas and one of the larger adenopathy. EUS also revealed an enlarged, non-nodular pancreas and a thickened duodenal wall. Mild ascites was detected. Both EUS-biopsies were concordant on the diagnosis of carcinoma with gastric or pancreatic-biliary origin, highly aggressive (Ki67 > 80 %). Therefore, the diagnosis of pancreatic adenocarcinoma was assumed (cT4N1Mx). The patient is currently on palliative chemotherapy and remains paucisymptomatic.