Prognosis of gastric cancer is dramatically improved by early diagnosis. Correa’s cascade correlates the expression of some molecular markers with the progression of preneoplastic lesions toward carcinoma. This article reviews the diagnostic and prognostic values of molecular markers in complete (MUC2) and incomplete (MUC2, MUC5AC, and MUC6) intestinal metaplasia, gastric dysplasia/intra-epithelial neoplasia, and early gastric cancer. In particular, considering preinvasive neoplasia and early gastric cancer, some studies have demonstrated a correlation between molecular alterations and prognosis, for example, mucins phenotype in gastric dysplasia, and GATA6, TP53 mutation/LOH and MUC6 in early gastric cancer. Moreover, this review considers novelties from the literature regarding the (immuno)histochemical characterization of diffuse-type/signet ring cell gastric cancer, with particular attention to clinical outcomes of patients. The aim of this review is the evaluation of the state of the art regarding suitable biomarkers used in the pre-surgical phase, which can distinguish patients with different prognoses and help decide the best therapeutic strategy.

Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer-related deaths in Europe. About 5% of metastatic CRC (mCRC) are characterized by high microsatellite instability (MSI) due to a deficient DNA mismatch repair (dMMR), and this condition has been related to a high sensitivity to immunotherapy, in particular to the Immune Checkpoint Inhibitors (ICIs). In fact, in MSI-H or dMMR mCRC, treatment with ICIs induced remarkable response rates and prolonged survival. However, the majority of mCRC cases are mismatch-repair-proficient (pMMR) and microsatellite-stable (MSS), and unfortunately these conditions involve resistance to ICIs. This review aims to provide an overview of the strategies implemented to overcome ICI resistance and/or define subgroups of patients with MSS or dMMR mCRC who may benefit from immunotherapy.

Introduction: Large rectal lesions can conceal submucosal invasion and cancer nodules. Despite the increasing diffusion of high-definition endoscopes and the importance of an accurate morphological evaluation, a complete assessment in this setting can be challenging. Endoscopic ultrasound (EUS) plays an established role in the locoregional staging of rectal cancer, although this technique has a tendency toward the over-estimation of the loco-regional (T) staging. However, there are still few data on contrast-enhanced endoscopic ultrasound (CH-EUS), especially if this ancillary technique may increase the accuracy for predicting invasive nodules among large rectal lesions. Material and Methods: Consecutive large (≥20 mm) superficial rectal lesions with high-definition endoscopy, characterized by focal areas suggestive for invasive cancer/2B type according to JNET classification, were considered for additional standardized evaluation via CH-EUS with Sonovue ©. Results: From 2020 to 2023, we evaluated 12 consecutive superficial rectal lesions with sizes ranging from 20 to 180 mm. This evaluation provided additional elements to support the therapeutic decision made. Lesions were treated with surgical (3/12) or endoscopic treatment (9/12) according to their morphology and CH-EUS evaluation. Conclusion: Contrast-enhanced endoscopic ultrasound can provide an additional evaluation for large and difficult-to-classify rectal lesions. In our experience, CH-EUS staging corresponded to the final pathological stages in 9/12 (75%) lesions, improving the distinction between T1 and T2 lesions. Larger prospective studies and randomized trials should be conducted to support and standardize this approach.

(1) Background. In the differential diagnosis between sarcomatoid carcinoma (SC) and sarcomatoid mesothelioma (SM), we aimed to investigate the role of Claudin-4 and BAP1, a panel recently used to distinguish conventional carcinoma from epithelioid mesothelioma. (2) Methods. We collected 41 surgical pleural biopsies of SM, 46 surgical resections of SC from different sites and 49 pleural biopsies of normal/hyperplastic mesothelium. All the cases were tested for Claudin-4 and BAP1 using immunohistochemistry. The statistical calculations of the sensitivity, specificity and positive and negative predictive values were performed. (3) Results: Claudin-4 was negative in 41/41 SMs, while it was positive in 18/36 (50.1%) SCs (eight diffusely, 10 focally) within their sarcomatous component. BAP1 was lost in 23/41 SMs, while it was regularly expressed in 46/46 SCs. All the cases of the normal/hyperplastic mesothelium were negative for Claudin-4 and retained the regular expression of BAP1. The Claudin-4 expression was useful for detecting SC (sensitivity, 39.1%; specificity, 100%) and the BAP1 loss was useful for diagnosing SM (sensitivity, 56.1%; specificity, 100%). (4) Conclusions. The staining for Claudin-4 and BAP1 exhibited a low/moderate sensitivity in diagnosing SC and SM (39.1% and 56.1%, respectively), but a very high specificity (100%). Claudin-4 was expressed only in SC and BAP1 loss was noted only in SM.