Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy represent the standard of care for hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (mBC). While clinical trials established their efficacy, real-world evidence on safety, dose adjustments, and outcomes remains limited. We conducted a prospective observational study including patients with HR+/HER2- mBC treated with palbociclib, ribociclib, or abemaciclib across three oncology units between 2019 and 2024. Data on adverse events, dose modifications, progression-free survival (PFS), and overall survival (OS) were collected and analyzed. Adverse events were reported in 77.5% of patients. Neutropenia was the most frequent adverse event with palbociclib and ribociclib, while diarrhea and hepatic toxicity predominated with abemaciclib. Pulmonary toxicity occurred in 19.1% of abemaciclib-treated patients, often in those previously irradiated. Median PFS and OS were 26.4 and 31.1 months, respectively. The occurrence of grade 3-4 adverse events correlated with improved OS (37.1 vs. 23.0 months, P  < 0.001). Dose reductions, required in more than 60% of patients, did not compromise efficacy; instead, they were associated with longer PFS and OS. Conversely, treatment discontinuation predicted worse outcomes. In real-world practice, CDK4/6i toxicities are frequent but manageable. Proactive toxicity management and timely dose adjustments are essential to sustain treatment benefit. Dose reductions may even improve outcomes, underscoring the value of individualized dosing strategies.

e22655 Background: Lynch syndrome (LS) is a germ pathogenic mutations involving DNA Mismatch Repair (MMR) genes and is associated with an increased risk of several malignancies including gastrointestinal, genitourinary, gynecologic, skin, and brain cancers. Despite immense advancement in the knowledge available regarding molecular basis of breast cancer development, no biomarker is used in disease management except BRCA1 and BRCA2. Human MSH6 protein is one of the most important mismatch repair proteins in the post-replicative DNA mismatch repair system (MMR)’s, and plays a core role in repairing mismatched DNA bases In the process of DNA mismatch binding dissociation, the encoded protein can heterodimerize with MSH2 to form mismatch recognition complex, and exchange ADP and ATP as bidirectional molecular switch. Functioning of mismatch repair proteins involves 2 central dimers MutLα (MLH1 and/or PMS2) and MutSα (MSH2 and/or MSH6). Intact MSH2 and MLH1 are compulsory to maintain the stability of MSH6 and PMS2 respectively. However, MLH1 and MSH2 stability can be maintained in the absence of MSH6 or PMS2 because role is compensated by other mismatch repair proteins. Therefore, expression analysis of particular proteins by immunohistochemistry can lead to precise estimation of affected mismatch repair deficiency. Mismatch repair deficient phenotype may be developed during chemotherapeutic treatment. Methods: From the Santa Maria alle Scotte Hospital registry, we retrospectively identified female patients with LS diagnosed showed by the detection of a germ heterozygous pathogenic or likely-pathogenic variant in MLH1, MSH2, MSH6 or PMS2 on molecular genetic testing within April 2017 to June 2025. We compared our sample size to SEER of 2017 NCI database. Results: Overall, 50 female patients with LS were identified. Of those, 13 (26%) had primary BC (95% CI 1.463% to 26.7189% Chi-squared 5.95 p<0.0001 ). Among the BC LS patients, 91% (12 ) have a hormone receptor positive tumor and BC is the only diagnosis of cancer to date. 7 patients (45%) with BC LS have germinal MSH6 mutation, 4 of 13 patient has MSH2 alteration. MSH2 and MS6 patients have a more aggressive breast cancer with local relapse disease and distant metastases. Median age at diagnosis is 54.5 years, median follow up is 8 years: All patients are still alive and under treatment. Conclusions: In our single institution analysis, 26 % of female patients with LS developed BC. Our study suggests that MSH6 and MH2 mutations are closely linked to the occurrence, progression and metastasis of breast cancer. Further investigation with prospective clinical studies with larger samples is warranted to validate our data.

OBJECTIVES:The prognostic significance of microsatellite instability (MSI) and HER2 status in advanced gastric cancer (AGC) treated with neoadjuvant or conversion chemotherapy (NAC) remains unclear. This study aimed to evaluate their impact on pathological response and survival outcomes in AGC patients undergoing NAC followed by surgery. METHODS:This single-center, retrospective observational study included 121 patients with gastric adenocarcinoma at clinical stage >cT2N0, defined as tumor invasion beyond the muscularis propria, nodal involvement, or both. Eligible patients received at least two cycles of NAC and underwent surgical resection. Adults without other malignancies and with biopsy samples available for molecular analysis were included. Data were obtained from a prospectively maintained surgical database. Imaging studies were reviewed by expert radiologists, and molecular analyses were performed in the pathology department. RESULTS:Among the 121 patients, MSI was identified in 6.6% and HER2 positivity in 9.9%. All MSI tumors were HER2 negative ( P  < 0.001). HER2 positivity was more frequent in intestinal-type tumors ( P  = 0.034) and was associated with better pathological response ( P  = 0.048). The 5-year overall survival (OS) rate was 44.7%, with a median OS of 42.6 months. Multivariate Cox regression identified tumor location in the upper third, residual tumor, nodal stage, Lauren diffuse-mixed histotype, and negative HER2 status as independent prognostic factors ( P  < 0.05). MSI status was not significantly associated with OS ( P  = 0.786), although a trend toward improved survival was observed in MSI-H patients. CONCLUSIONS:HER2 overexpression correlated with better pathological response and independently predicted improved OS. MSI and HER2 status may serve as biomarkers to guide preoperative treatment strategies in AGC.

Background: PIPAC is an innovative treatment that delivers low-dose aerosolized chemotherapy into the abdominal cavity of patients with peritoneal surface malignancies (PSMs). However, its role in the multimodal management of PSMs is unclear. Methods: We retrospectively analyzed data from 64 patients who underwent PIPAC for PSMs of a primary or secondary origin between June 2020 and December 2024 (median age of 64 years). Primary tumor sites included gastric (42.2%), colorectal (23.4%), ovarian cancer (21.9%), and others (12.5%). The median PCI was 15 (IQR 9-25), with ascites present in 60.9% of cases and a positive cytology in 48.4%. Results: A total of 82 PIPAC sessions were performed in 64 patients. The mean operation time was 96 min. Severe adverse events, defined as the Common Terminology Criteria for Adverse Events (CTCAE) of a grade ≥ 2, occurred in four patients (6.2%). The median hospital stay was 3 days, and systemic chemotherapy was resumed within 14 days after the procedure in 27 patients. Among the entire cohort, 37.5% received bidirectional therapy and 62.5% received palliative treatment, with a lower peritoneal cancer index (PCI) in the bidirectional group (9.5 vs. 23). The median overall survival (OS) was 32 months from diagnosis. Sixteen patients (25%) underwent two or more PIPAC sessions and showed an advantage in survival compared to patients who underwent only one procedure (3-year OS: 63.2% vs. 38.4%, p 0.030). Conversion surgery was achieved in 34.4%. Patients treated with a bidirectional intent demonstrated a longer OS (3-year: 66.0% vs. 33.9%, p 0.011). Colorectal and ovarian tumors exhibited better long-term outcomes compared to gastric cancer. Conclusions: PIPAC is a promising treatment for PSMs, with a low morbidity rate. Its favorable safety and short interval to systemic therapy resumption support its use as part of a bidirectional strategy.

Neurofibromatosis type 1 (NF1) is a rare genetic disorder with highly variable phenotypes, ranging from psychosocial challenges and congenital malformations to benign tumors and even aggressive cancers. We hypothesize that this variability stems from additional rare variants in other genes, in addition to NF1 variants. The analysis of 32 NF1 patients revealed that those with solid cancers carried a higher average of cancer driver variants especially in DNA repair genes compared to those without (p < 0.05). An extended validation study using 217 NF1 carriers (71 cancer and 146 controls) from UK biobank confirmed significant enrichment of pathogenic (P), likely pathogenic (LP) and uncertain significant (VUS) variants in DNA repair genes, in NF1 patients with tumors (FDR ≤ 0.05). Furthermore, P/LP variants in other genes are shown in those patients with NF1 ancillary traits such as cognitive impairments, macrocephaly, and connective defects. This study provides novel evidence suggesting that additional genetic variants in other genes may contribute to the phenotypic variability observed in NF1, indicating that rare secondary mutational events could influence specific manifestations, adding complexity to its variable expressivity.

CDK4/6 inhibitors have transformed treatment for HR + HER2 − advanced breast cancer (aBC). However, adverse events (AEs) often lead to dose adjustments or discontinuation, potentially impacting outcomes. This study assessed AE incidence and its effect on survival in patients receiving abemaciclib (AB), ribociclib (RB), or palbociclib (PB). A retrospective study of 162 h + HER2 − aBC patients treated with CDK4/6 inhibitors as first-line therapy (July 2017–September 2024) was conducted. AE incidence, progression-free survival (PFS), and overall survival (OS) were analyzed. Most patients (91.4

Super-extended (D2plus) lymphadenectomy after chemotherapy has been reported in only a few studies. This retrospective study evaluates survival outcomes in a Western cohort of locally advanced or oligometastatic gastric cancer patients who underwent D2plus lymphadenectomy after neoadjuvant chemotherapy. A total of 97 patients treated between 2010 and 2022 were included. Of these, 62 had clinical stage II/III disease, and 35 had stage IV disease. Most patients (65%) received preoperative DOC/FLOT chemotherapy. The mean number of lymph nodes harvested was 39. Pathological positive nodes in the posterior/para-aortic stations occurred in 17 (17.5%) patients. Lymphovascular invasion, ypN stage, clinical stage, and perineural invasion were predictive factors for positive posterior/para-aortic nodes. Postoperative complications occurred in 21 patients, whereas severe complications (grade III or more) occurred in 9 cases (9.3%). Mortality rate was 1%. Median overall survival (OS) was 59 months (95% CI: 13–106), with a five-year survival rate of 49 ± 6%; the five-year OS after R0 surgery was 60 ± 7%. In patients with positive posterior/para-aortic nodes, the median OS was 15 months (95% CI: 13–18). D2plus lymphadenectomy after chemotherapy for locally advanced or oligometastatic gastric cancer is feasible and associated with low morbidity/mortality rates. The incidence of pathological metastases in posterior/para-aortic nodes is not negligible even after systemic chemotherapy, with poor long-term survival.

Introduction: Urachal carcinoma accounts for approximately 0.01 % of all adult malignancies and 1 % of bladder cancers. Its prognosis remains poor, with a 5 -year overall survival rate of less than 50 %. Presentation of case: A 51 -years -old black female, affected by peritoneal malignancies from urachal carcinoma, underwent multiple surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with different chemotherapy regimen, alternating with intravenous chemotherapy. Thirty-two months recurrence -free survival was registered, and overall survival was more than 5 years. Discussion: Our case suggests the importance of rigorous follow-up with both tumor marker testing (CEA) and imaging studies. Optimal debulking surgery plays a pivotal role in controlling primary and recurrent disease. The use of combined intraperitoneal and intravenous chemotherapy may have contributed to her long-term survival. Conclusion: CRS and HIPEC combined with intravenous chemotherapy may be potential candidates for treating patients with urachal carcinoma with peritoneal metastases. Our patient is a challenging case in daily surgical practice.

BACKGROUND: Gastro-entero-pancreatic neuroendocrine tumors are gradually seeing their incidence increase, probably due to their low-rate mortality. Surgery and subsequent medical therapy through octeotride and somatostatin analogues is the recommended approach forhy persecretive hormonal forms, showing an effective control of symptoms and improved survival outcomes. AIM: The present study aims to evaluate the occurrence of gallbladder lithiasis, and its complications, in patients under-went upfront surgery for neuroendocrine tumors and subsequent long-term administration of somatostatin analogues. MATERIAL OFSTUDY: We included four adults affected by neuroendocrine (gastric, appendiceal and ileal) tumors andwithout previous evidence of gallbladder stones, who needed an emergency cholecystectomy after long-term somatostatintreatment. RESULTS: The patients showed complicated conditions sustained by cholelithiasis, such as acute cholecystitis, gangrenouscholecystitis, or intestinal occlusion, which required emergency surgery. DISCUSSIONS: Somatostatin analogues may influence the cascade of enzymes that guarantee the gallbladder motility, and consequently cause the precipitation of cholesterol and calcium bilirubinate crystals. Therefore, higher and sustained levels of somatostatin may result in higher rates of gallstone development. CONCLUSIONS: The prophylactic cholecystectomy, during upfront surgery for neuroendocrine tumors, might prevent an emergency cholecystectomy for gallstones complications

Aim: To investigate the impact of natremia in metastatic colorectal cancer (mCRC) patients treated with aflibercept plus folinic acid, 5-fluorouracil, oxaliplatin and irinotecan (FOLFIRI). Patients & methods: A total of 84 mCRC patients receiving aflibercept plus FOLFIRI as second-line treatment were enrolled and divided into two groups based on their median sodium value. Progression-free survival and overall survival were analyzed. Results: Patients with sodium levels ≥140 mEq/l had significantly longer median progression-free survival (4.1 vs 2 months; p < 0.01) and median overall survival (12 vs 7.3 months; p < 0.01) compared with those with lower levels. Conclusion: This study suggests that higher pretreatment serum sodium levels are associated with improved outcomes in mCRC patients receiving aflibercept and FOLFIRI, potentially serving as a prognostic marker to aid treatment management.

BACKGROUND:With the availability of multiple treatment options for metastatic castration-resistant prostate cancer (mCRPC), new real-world data on disease management and drugs' performance are needed.METHODS:We described characteristics, management and clinical outcomes of patients receiving first-line mCRPC treatment within the Italian cohort of the real-world, prospective, international Prostate Cancer Registry. Patients were enrolled consecutively (2013-2016) in 32 Italian sites and followed for 3 years.RESULTS:238 patients were included: 157 received first-line abiraterone acetate plus prednisone ("abiraterone" thereafter) and 70 first-line docetaxel; 11 patients receiving other treatments were not considered. Compared with docetaxel-treated patients, those receiving abiraterone were significantly older (age ⩾75: 63.7% vs 38.6%), less frequently had a Gleason score >8 (48.2% vs 67.6%, p<0.005) at initial diagnosis, and more frequently an ECOG score ⩾1 (52.7% vs 36.2%, p<0.05) and comorbidities (76.4% vs 57.1%, p<0.05) at baseline; they reported a lower analgesic use (15.3% vs 30%, p<0.005). In the abiraterone group (median follow-up 22.1 months), median time to progression (TTP) and progression-free survival (PFS) were, respectively, 14.4 months (95% confidence interval, CI, 10.6-18.0) and 13.0 months (95% CI, 9.1-16.8); median overall survival (OS) was not reached, and 3-year OS was 59.1%. In the docetaxel treatment group (median follow-up 25.3 months), median TTP, PFS and OS were, respectively, 8.2 months (95% CI, 6.1-10.3), 8.2 months (95% CI, 5.8-10.3) and 33.2 months (95% CI, 19.2-not estimable).CONCLUSION:This investigation provided valuable information on the overall mCRPC treatment pattern and the effectiveness of first-line abiraterone and docetaxel in a population representative of everyday practice.

Background: Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. This study evaluated the prognostic role of serum alanine phosphatase (ALP) and gamma-glutamyl-transferase (GGT) in metastatic PC patients. Materials & methods: 153 patients with metastatic PC receiving first-line treatment with nab-paclitaxel/gemcitabine were retrospectively enrolled in a multicenter study and stratified according to ALP (≤ or >260 U/l) and GGT (≤ or >45.5 U/l) levels. Results: Improved overall survival was recorded in patients with GGT levels ≤45.5 U/l (p < 0.05). In patients with liver metastasis, overall survival was significantly lower in patients with high ALP (p = 0.01) and GGT (p = 0.02). Conclusion: High levels of ALP and GGT were related to a poor prognosis in PC patients with liver metastasis receiving nab-paclitaxel/gemcitabine.

e22549 Background: Lynch syndrome (LS) is associated with an increased risk of several malignancies including gastrointestinal, genitourinary, gynecologic, skin, and brain cancers. However, whether patients with LS have higher risk of developing breast cancer (BC) or not is still controversial and a relevant clinical question. Methods: From the Santa Maria alle Scotte Hospital registry, we retrospectively identified consecutive patients with LS diagnosed by detecting a germline heterozygous pathogenic or likely-pathogenic variant in MLH1, MSH2, MSH6 or PMS2 on molecular genetic testing within April 2016-January 2022. We compared our sample size to Surveillance, Epidemiology, and End Results Program (SEER) of 2017 National Cancer Institute database. Results: Overall, 43 patients with LS were identified. Of those, 11 (25.6%; 95% CI 1.58-26.72%; p < 0.0001) had histologically confirmed BC, 10 (91%) of whom were hormone receptor positive tumors and BC is the only diagnosis of cancer to date. In this 11 patients median age at diagnosis was 54.5 years. 45% of 11 BC LS patients has germinal MSH2 mutation , 45% of 11% are MSH6 mutaded and has a more aggressive breast cancer. Median follow-up was 3 years and 8 months. All patients are still alive and under treatment. Conclusions: Within the limitations of a small sample size and retrospective design, our analysis suggests a significant association between patients with LS and the diagnosis of primary BC. Validation of such findings through prospective clinical studies with larger samples is warranted and would lead to fundamental modifications to LS screening and follow-up international recommendations.

Over the years the treatment strategy of gastric cancer (GC) has been modified to improve clinical outcome. Neoadjuvant and perioperative therapies are emerging as the new standard of care in the setting of locally advanced disease, with systemic treatment performed also before surgery. At the same time, the molecular and biological aspects of disease are becoming important factors conditioning the results. Conducted studies confirm the improvement in the long-term prognosis of operable GC with neoadjuvant or perioperative strategy. To date, we have no clear data to identify the best strategy to be used, so it is necessary to design studies that integrate clinical and biological variables for GC to improve knowledge and better define treatment strategies.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent adverse events observed with taxane use, whose disability often required modification or treatment discontinuation. The aim of this study was to assess the value of several variables as risk factors for CIPN development. Material and Methods: Eligible patients with metastatic pancreatic cancer receiving chemotherapy with nab-paclitaxel and gemcitabine were assessed in a multicenter study. Peripheral neuropathy was categorized using the National Cancer Institute Common Toxicity Criteria scale, version 4.02, and a physical/neurological examination. Univariate and multivariate regression analyses were used to identify blood-based and clinical factors associated with CIPN. Results: Data were available from 153 patients from five Italian centers. Key risk factors of CIPN in univariate regression models included age, number of chemotherapy cycles, statin assumption, and concomitant comorbidities. However, in the multivariate analysis, only for age (OR 1.0, p < 0.01, 95% CI: 1.01–1.11) and the number of cycles (OR 1.22, p < 0.01, 95% CI: 1.09–1.36), the correlation with CIPN development has been confirmed. Conclusion: Our study confirms age and the number of chemotherapy cycles as CIPN risk factors. The identification and validation of different risk factors could be advantageous to prevent or optimize management of CIPN which outstandingly affect the patient’s quality of life.

Background and ObjectivesOnly recently the percentage of signet ring cells (SRCs) in gastric cancer (GC) has been proposed as an independent predictor of survival. High amounts of SRCs have been related to lower recurrence and mortality rates, better prognosis, and favorable clinicopathological features in a poorly cohesive histotype. It is not known what the effect of SRC percentage in mixed-type GC is. We investigate the role of SRCs as a prognostic marker in mixed-histotype GC.MethodsA retrospective analysis was performed through a prospectively maintained database of patients with diagnosed “mixed-type” gastric carcinoma, defined according to 2019 WHO classification. These patients underwent surgery between 1995 and 2016, and their tissue samples were stored in a tissue bank. All slides were analyzed, and patients were divided into three groups according to the percentage of SRCs: “Group 1” (displaying ≤10% of SRCs), “Group 2” (displaying <90% but >10% of SRCs), and “Group 3” (displaying ≥90% of SRCs). We compared clinical and pathological features as well as prognostic factors between the different groups.ResultsAmong 164 enrolled patients, 68.9% were male and 31.1% were female (p = 0.612). The mean (±SD) age at diagnosis was 71.4 ± 9.6 years. Ninety-eight (59.7%) patients were classified as “Group 1”, 66 (40.3%) as “Group 2”, and none as “Group 3”. Five-year overall survival was remarkably higher in Group 2 (73.8%) in comparison to Group 1 (35.4%), p < 0.001. Mortality risk was three times higher in patients with ≤10% SRC pattern compared to those with >10% [HR 2.70 (95% CI 1.72–4.24)]. After adjusting according to potential confounding factors, SRC percentage was still an independent predictor of survival.ConclusionsThe proportion of SRCs is inversely related to aggressive behavior and poor prognosis in mixed-type GCs, highlighting the role of SRC amount as an independent predictor of survival.

Few studies have evaluated the impact of risk factors such as performance status (PS) and comorbidities on overall survival (OS) in patients with metastatic pancreatic cancer (mPC). We investigated the influence of comorbidity, PS and age on nab-paclitaxel and gemcitabine (NabGem) effectiveness profile in naive patients with mPC. 153 patients with mPC treated with NabGem upfront was divided in three groups (score 0 to 3) based on the absence or the presence of one or more risk factors among: age ≥ 70 years, PS 1 and comorbidities and the clinical outcomes was compared. Fifty-five patients were elderly (≥ 70 years), 80 patients have PS 1, whereas the other have PS 0. Patients with no risk factors (score 0) had an overall survival higher (20 months) than patients with one or two risk factors (score 1–2) (OS 11 months) and with three risk factors (score 3) (OS 8 months) ( p < 0.01). The difference in OS was also statistically significant in patients without comorbidities (OS 15 months) compared to those with ≥ 1 comorbidity (OS 10 months) ( p < 0.001). NabGem chemotherapy represent an effective treatment in naive patients. Age, PS, and comorbidities were prognostic factors in patients with metastatic pancreatic cancer.

Angiogenesis supplies for increased request of oxygen and nutrients which is typical of the fast-growing microenvironment of solid tumors. Tumor angiogenesis provides for the formation of new blood vessels in an uncontrolled and not-organized fashion, ultimately resulting in enhanced tumor growth and increased metastatic potential. The angiogenetic mechanism represents an appealing target for novel anticancer therapies and several antiangiogenic drugs are available for the treatment of some tumor types. Herein, we summarize the clinical evidence supporting the use of antiangiogenic agents in patients with colorectal cancer and the promising activity of antiangiogenic drugs, alone or combined with conventional therapy, exhibited in patients with advanced gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJ). The antiangiogenic drug bevacizumab combined with conventional chemotherapy was effective in increasing the median OS of patients with metastatic colorectal cancer. Nevertheless, although the inhibition of angiogenesis became an interesting area of GC research, the role of antiangiogenic agents remains controversial in this tumor type. The antiangiogenic agent ramucirumab was the first and unique antiangiogenic drug which was approved for the treatment of metastatic GC patients after failure of first-line treatment. Several oral multi-target tyrosine kinase inhibitors (TKI) were investigated in advanced GC and GEJ adenocarcinoma, and some of these agents (sunitinib, sorafenib, apatinib, trebananib, and regorafenib) achieved encouraging results in terms of PFS and OS. Recently, the combination of antiangiogenic agents plus immunotherapy exhibited promising results in patients with advanced GC or GEJ adenocarcinoma. The ongoing trials will help to clarify the real efficacy of the combination of antiangiogenic agents with conventional anticancer treatment and with immune checkpoint inhibitors (ICIs) in advanced GC and GEJ adenocarcinoma, and the role of predictive and prognostic biomarkers.

Background: Although the prognostic value of the epithelial-to-mesenchymal transition (EMT) in gastric cancer has been reported in several studies, the strong association with the diffuse type may represent a confounding factor. Our aim is to investigate potential correlations among EMT status, tumor advancement, and prognosis in diffuse gastric cancer. Methods: Between 1997 and 2012, 84 patients with microsatellite-stable (MSS) diffuse-type tumors underwent surgery. The EMT phenotype was assessed with the E-cadherin, CD44, and zinc finger E-box binding homeobox 1 (ZEB-1) immunohistochemical markers. Results: Forty-five out of 84 cases (54%) were EMT-positive; more advanced nodal status (p = 0.010), pTNM stage (p = 0.032), and vascular invasion (p = 0.037) were observed in this group. The median numbers of positive nodes (13 vs. 5) and involved nodal stations (4 vs. 2) were higher in the EMT-positive group. The cancer-related survival time was 26 months in EMT-positive cases vs. 51 in negative cases, with five-year survival rates of 17% vs. 51%, respectively (p = 0.001). The EMT status had an impact on the prognosis of patients with <70 years, R0 resections, or treatment with adjuvant chemotherapy. Tumor relapses after surgery and peritoneal spread were significantly higher in the EMT-positive tumors. Conclusions: EMT status, when assessed through immunohistochemistry, identified an aggressive phenotype of MSS diffuse-type tumors with extensive lymph nodal spread, peritoneal dissemination, and worse long-term outcomes.

Background and objectives: Signet ring cells (SRC) are widely acknowledged as a prognostically unfavorable histotype amongst poorly cohesive gastric cancer. In this study we evaluated the impact of SRC percentage on the clinical, pathological and prognostic features of these tumors according to the classification by the European Chapter of the IGCA. Methods: We retrospectively reviewed records of patients with poorly cohesive gastric cancer that underwent surgery between 1995 and 2016, whose tissue specimens were available in a biological bank. All slides were put under revision, patients were reclassified into three groups according to the proportion of signet ring cells: "pure" SRC (containing >90% of SRCs), Poorly Cohesive-Not Otherwise Specified (PC -NOS) (containing <10% of SRCs), and PC-NOS/SRC (containing <90% but >10% of SRCs). The clinicopathological factors between different types were analyzed and prognostic differences were compared. Results: Among 143 enrolled patients, 51% were male and 49% were female. The mean (+/- SD) age at diagnosis was 61 +/- 13.9 years. Eighty-seven patients (60.8%) were reclassified as PC-NOS, 56 (39.2%) as PC-NOS/SRC and none as "pure" SRC. Five-years overall survival was significantly higher in PC-NOS/SRC group (63.3%) compared with PC-NOS group (12.7%). The increase in mortality risk was more than fourfold in patients with PC-NOS pattern compared to those with PC-NOS/SRC (HR 4.32 [95% CI 2.5-7.4]. After adjustment for potential confounding factors, SRC pattern was still an independent predictor of survival. Conclusions: The percentage of SRCs is inversely related to tumor aggressiveness, confirming the role of SRC pattern as an independent predictor of survival. (c) 2021 Elsevier Ltd, BASO - The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.