Proteomic heterogeneity of the extracellular matrix identifies histologic subtype-specific fibroblast in gastric cancer.

Gastric cancer (GC) is a highly heterogeneous disease regarding histologic features, genotypes, and molecular phenotypes. Here, we investigate extracellular matrix (ECM)-centric analysis, examining its association with histologic subtypes and patient prognosis in human gastric cancer. We performed quantitative proteomic analysis of decellularized GC tissues that characterizes tumorous ECM, highlighting proteomic heterogeneity in ECM components. We identified 20 tumor-enriched proteins including four glycoproteins, serpin family H Member 1 (SERPINH1), Annexin family (ANXA3/4/5/13), S100A family (S100A6/8/9), MMP14, and other matrisome-associated proteins. In addition, histopathological characteristics of GC reveals differential expression in ECM composition, with the poorly cohesive carcinoma not otherwise specified (PCC-NOS) subtype being distinctly demarcated from other histologic subtypes. Integrating ECM proteomics with single-cell RNA sequencing, we identified crucial molecular markers in the PCC-NOS-specific stroma. PCC-NOS-enriched matrisome proteins (PEMs) and gene expression signatures of adipogenic cancer-associated fibroblasts (CAFadi) are closely linked, both associated with adverse outcomes in GC. Using tumor microarray analysis, we confirmed the CAFadi surface marker, ATP binding cassette subfamily A member 8 (ABCA8), predominantly present in PCC-NOS tumors. Our ECM-focused analysis paves the way for studies to determine their utility as biomarkers for patient stratification, offering valuable insights for linking molecular and histologic features in GC.

IFIT1 + neutrophil is a causative factor of immunosuppressive features of poorly cohesive carcinoma (PCC).

The importance of the immune microenvironment in poorly cohesive carcinoma (PCC) has been highlighted due to its limited response rate to conventional therapy and emerging treatment resistance. A combination of clinical cohorts, bioinformatics analyses, and functional/molecular experiments revealed that high infiltration of Interferon Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) + tumor-associated neutrophils (TANs) is a distinguishing feature of PCC patients. Upregulation of IFIT1 + TANs promote migration and invasion of gastric cancer (GC) cell lines (MKN45 and MKN74) and stimulates the growth of cell-derived xenograft models. Besides, by promoting macrophage secreted phosphoprotein 1 (SPP1) expression and facilitating cancer-associated fibroblast and endothelial cell recruitment and activation through TANs, IFIT1 promotes a mesenchymal phenotype, which is associated with a poor prognosis. Importantly, compared to non-PCC (NPCC), PCC tumors is more immunosuppressive. Mechanistically, IFIT1 can be stimulated by IFN-γ and contributes to the expression of Programmed Cell Death 1 Ligand (PDL1) in TANs. We demonstrated in mouse models that IFIT1 + PDL1 + TANs can induce acquired resistance to anti-PD-1 immunotherapy, which may be responsible for the difficulty of PCC patients to benefit from immunotherapy. This work highlights the role of IFIT1 + TANs in mediating the remodeling of the tumor immune microenvironment and immunotherapeutic resistance and introduces IFIT1 + TANs as a promising target for precision therapy of PCC.

Total Versus Subtotal Gastrectomy for Distal Gastric Poorly Cohesive Carcinoma.

BACKGROUND: Gastric poorly cohesive carcinoma (PCC) in advanced stages has a poor prognosis. Total gastrectomy (TG) remains the common treatment for distal gastric PCC, but subtotal gastrectomy (SG) may improve quality of life without compromising outcomes. Currently, no clear recommendation on the best surgical strategy for distal PCC is available. This study aimed to compare overall survival (OS) and disease-free survival (DFS) at 5 years for patients with antropyloric PCC treated by total versus subtotal gastrectomy. METHODS: A large retrospective European multicenter cohort study analyzed 2131 patients treated for gastric cancer between 2007 and 2017 by members of the French Association of Surgery (AFC). The study compared a group of patients who underwent TG with a group who underwent SG for antropyloric PCC. The primary outcomes were 5 year OS and DFS. RESULTS: The study enrolled 269 patients: 140 (52.0%) in the TG group and 129 (48.0%) in the SG group. The baseline characteristics and pTNM stage were similar between the two groups. According to Dindo-Claven classification, the patients treated with TG had more postoperative complications than the patients treated with SG (p < 0.001): grades I to IIIa (77.1% vs 59.5%) and grades IIIb to IVb (14.4% vs 9.0%). No difference in 5-year OS was observed between TG (53.8%; 95 % confidence interval [CI], 43.2-63.3%) and SG (53.0%; 95% CI, 41.4-63.3%) (hazard ratio [HR], 0.94; 95% CI, 0.68-1.29). The same was observed for 5-year DFS: TG (46.0%; 95% CI, 35.9-55.5%) versus SG (45.3%; 95% CI, 34.3-55.6%) (HR, 0.97; 95% CI, 0.70-1.34). CONCLUSIONS: At 5 years, SG was not associated with worse OS and DFS than TG for distal PCC. Surgical morbidity was higher after TG. Subtotal gastrectomy is a valuable option for distal PCC gastric cancer.

USP51/ZEB1/ACTA2 axis promotes mesenchymal phenotype in gastric cancer and is associated with low cohesion characteristics.

poorly cohesive (PC) gastric cancer (GC) (PC-GC) is a distinct histological subtype of GC and is defined as a tumor consisting of isolated or small clusters of tumor cells with poorly differentiated and metastatic characteristics. According to multiple studies, PC-GC is intrinsically heterogeneous, with mesenchymal variants being the most aggressive. However, to date, the molecular mechanisms associated with PC-GC are still not fully understood. This study investigated the role of the USP51/ZEB1/ACTA2 axis in promoting GC metastasis. Single-cell sequencing revealed that E-box binding homeobox 1 (ZEB1) expression was significantly increased in a subpopulation of low-adherent cells and was an independent prognostic factor in GC patients. Furthermore, the bulk transcriptome analysis revealed a significant positive correlation between Ubiquitin Specific Peptidase 51 (USP51), ZEB1, and Actin Alpha 2 (ACTA2), and our data further confirmed that all three were highly co-localized in PC-GC tissues. According to the findings of in vitro and in vivo experiments, USP51 was able to maintain ZEB1 expression to promote ACTA2 transcription, thereby activating the mesenchymal phenotype of GC cells and promoting tumor metastasis. Moreover, USP51 could recruit and activate stromal cells, including M2-like macrophages and fibroblasts, through cancer cells. Clinical data suggested that overexpression of USP51 predicts that patients have difficulty benefiting from immunotherapy and is associated with immune-exclusion tumor characteristics. Collectively, the findings of this study shed light on a key mechanism by which elevated USP51 expression induces Epithelial-mesenchymal transition (EMT) in GC cells, hence facilitating GC cell proliferation, survival, and dissemination. In this view, USP51/ZEB1/ACTA2 may serve as a candidate therapeutic target against GC metastasis.

Clinicopathological characteristics and prognosis of poorly cohesive cell subtype of gastric cancer.

BACKGROUND: The new World Health Organization (WHO) classification of gastric cancer includes a histological subtype of poorly cohesive carcinoma (PCC), which includes signet-ring cell (SRC) phenotype. We aimed to examine the concordance between preoperative clinical and postoperative histological diagnoses according to the 2010 WHO histological subtypes and to compare the prognoses of these subtypes. METHODS: The study cohort comprised 665 patients who underwent gastrectomy from 2005 to 2019. Histological subtypes were classified into PCC-NOS (non-signet ring cell subtype), SRC, and non-PCC, which were defined by the predominant component in accordance with the 2010 WHO classification of gastric cancer. The concordance of clinical and pathological diagnosis was examined and clinicopathological characteristics and survival outcome of the three subtypes compared. RESULTS: The cancers of 443 patients (66.7%) were classified as non-PCC, of 112 patients (16.8%) as PCC-NOS, and of 110 patients (16.5%) as SRC predominant subtypes. Significant differences in sex, age, tumor location, size, macroscopic type, and pathological TNM category (all P<0.05) were found. The concordance rate of preoperative and postoperative histological subtypes was significantly lower for poorly cohesive than other subtypes (P<0.0001). Preoperative stage tended to be underestimated for PCC-NOS subtype and these patients had poorer overall survival than those with the other two subtypes (P=0.005). Multivariate logistic regression analysis of overall survival showed that WHO histological subtype (PCC-NOS vs. non-PCC/SRC, HR: 1.64, 95% CI: 1.18-2.29, P=0.0034) was a significant independent prognostic factor. CONCLUSION: Our results suggest that poorly cohesive carcinoma subtypes have different biological characteristics and prognoses.

[Poorly cohesive gastric carcinoma. Validity of using the term; translation variants]. / Kartsinoma zheludka iz plokho stseplennykh kletok. Pravomochnost' ispol'zovaniya termina i varianty perevoda.

Gastric cancer is one of the leading causes of cancer morbidity and mortality worldwide. It is common practice to use two classification systems: the Lauren classification system and the WHO classification of tumors in the morphological study of gastric carcinomas. Since 2010, the WHO classifications have included the term "poorly cohesive carcinoma", which refers to all diffuse forms of gastric cancer, including signet ring cell carcinoma and other subtypes. Despite this, the term has not been widely used in the world community, and it is almost not found in Russian literature. Only recently, after the publication of the 5th edition of the WHO classification (2019), there have been review articles where the term is used, but its name can be translated into Russian in different ways: poor-, weak -, low-adhesive, discogesive. The paper analyzes the Pubmed and Elibrary databases in order to find out the frequency of using various designations for diffuse gastric carcinoma, justifies the use of the term «poorly cohesive carcinoma¼, and proposes a variant of the term interpretation in Russian.

[Changes in the classification of malignant colon epithelial neoplasms. (WHO, 2019, 5th edition)]. / Novoe v klassifikatsii zlokachestvennykh epitelial'nykh opukholei tolstoi kishki. (VOZ, 2019, 5-e izdanie).

There are not many changes compared to 2010 in WHO classification (2019) of colon adenocarcinomas. Cribriform comedo-type adenocarcinoma (ICD-O code: 8201/3), spindle cell carcinoma (8032/3), squamous cell carcinoma (8070/3) are excluded; carcinoma with a sarcomatoid component (8033/3), poorly cohesive carcinoma (8490/3) and adenoma-like adenocarcinoma (8262/3) were added. The important histological characteristics in the conclusion should indicate the presence of lymphatic invasion, intra- and extramural vascular invasion, perineural invasion, grading, «tumor budding¼ and the immune microenvironment. In the 5th edition of the classification a large section has been added regarding molecular diagnostics and molecular prognostic factors of colorectal cancer. Correspondence was found between two different classifications based on two different approaches: genomic (according to DNA analysis) and transcriptomic (according to RNA analysis). According to the genomic classification two large groups of colorectal cancer are distinguished: hypermutated and non-hypermutated cancers that correspond to molecular pathways with the development of microsatellite and chromosomal instabilities, respectively. The section of neuroendocrine tumors did not undergo significant changes. It is not recommended to use the term «carcinoid¼ to refer to a neuroendocrine tumor G1, that is, the term «carcinoid¼ is excluded.

Gastric poorly cohesive carcinoma: a correlative study of mutational signatures and prognostic significance based on histopathological subtypes.

AIMS: Genome-wide next-generation sequencing has revealed several driver mutations and has allowed the establishment of a molecular taxonomy of gastric cancer. However, there are few detailed studies on the mutational spectrum of poorly cohesive gastric carcinoma. Thus, this study aim to investigate its mutation profile based on clinicopathological characteristics. METHODS AND RESULTS: Herein, we analysed the mutational pattern of 77 genes in a cohort of 91 patients with poorly cohesive carcinoma by using targeted sequencing, and evaluated the clinicopathological significance of the various mutations based on histological pattern, either signet ring cell (SRC) or other types of poorly cohesive carcinoma (not otherwise specified) (PCC-NOS). Panels of seven (PIK3CA, CDH1, PTEN, RHOA, HDCA9, KRAS, and ATM), three (PIK3CA, CTNNB1, and KRAS) and two (HDCA9 and IGF1R) genes were associated with a diffuse infiltrative growth pattern, lymphovascular invasion, and perineural invasion, respectively. Furthermore, PDGFRB mutations were associated with a favourable prognosis, whereas MET mutations were associated with a poor prognosis. The PCC-NOS-predominant type was associated with a greater depth of invasion, lymph node metastasis and poorer prognosis than the SRC-predominant type. Mutations in TP53, BRAF, PI3CA, SMAD4 and RHOA were associated with PCC-NOS. Interestingly, RHOA-mutated gastric cancers showed a distinct morphology, as they were characterised by a superficial SRC or tubular component and a deep invasive PCC-NOS component with desmoplasia. CONCLUSIONS: Taken together, our findings demonstrate that gastric poorly cohesive carcinomas show several mutational patterns associated with specific clinicopathological characteristics, and particularly show distinct morphological findings when associated with RHOA mutation.

CT Perfusion evaluation of gastric cancer: correlation with histologic type.

OBJECTIVES: To prospectively evaluate if the perfusion parameters of gastric cancer can provide information on histologic subtypes of gastric cancer. METHODS: We performed preoperative perfusion CT (PCT) and curative gastrectomy in 46 patients. PCT data were analysed using a dedicated software program. Perfusion parameters were obtained by two independent radiologists and were compared according to histologic type using Kruskal-Wallis, Mann-Whitney U test and receiver operating characteristic analysis. To assess inter-reader agreement, we used intraclass correlation coefficient (ICC). RESULTS: Inter-reader agreement for perfusion parameters was moderate to substantial (ICC = 0.585-0.678). Permeability surface value of poorly cohesive carcinoma (PCC) was significantly higher than other histologic types (47.3 ml/100 g/min in PCC vs 26.5 ml/100 g/min in non-PCC, P < 0.001). Mean transit time (MTT) of PCC was also significantly longer than non-PCC (13.0 s in PCC vs 10.3 s in non-PCC, P = 0.032). The area under the curve to predict PCC was 0.891 (P < 0.001) for permeability surface and 0.697 (P = 0.015) for MTT. CONCLUSION: Obtaining perfusion parameters from PCT was feasible in gastric cancer patients and can aid in the preoperative imaging diagnosis of PCC-type gastric cancer as the permeability surface and MTT value of PCC type gastric cancer were significantly higher than those of non-PCC. KEY POINTS: • Obtaining perfusion parameters from PCT was feasible in patients with gastric cancer. • Permeability surface and MTT were significantly higher in poorly cohesive carcinoma (PCC). • Permeability surface, MTT can aid in the preoperative imaging diagnosis of PCC.

Poorly cohesive gastric cancer with increased epithelial­mesenchymal transition is associated with a poor prognosis.

The present study examined the surgical outcome and prognosis of patients with poorly cohesive carcinoma (PCC), and characterized the molecular pathological factors, epithelial-mesenchymal transition (EMT) and interstitial signals of the disease. A total of 281 patients who underwent gastric cancer (GC) surgery between April 2015 and August 2020 were included. Furthermore, tissue samples from another 197 patients with GC who underwent surgery between 1999 and 2003 were assessed using a tissue microarray. Preoperatively treated cases and endoscopic submucosal dissection cases were excluded, and multiple blocks containing the invasion region were collected for tissue microarray. For tissue microarray analysis, the clinicopathological factors of protein wnt3a (wnt3a), leucine-rich repeat-containing G-protein coupled receptor 5, transforming growth factor-ß-induced, phosphorylated serine/threonine-protein kinase mTOR and E-cadherin expression were collected as EMT markers. The results of the surgical case evaluation and tissue microarray indicated that PCC was more common in younger patients and women, as the ratio of women to men was higher in the PCC group compared with that in the non-PCC group. However, none of the results revealed that the prognosis was worse in all patients with PCC compared with the non-PCC group. Furthermore, in the tissue microarray study, PCC samples exhibited significantly decreased expression of the cell adhesion molecule E-cadherin, suggesting enhanced EMT, which activates wnt3a signaling. PCC with increased EMT was significantly associated with a poor prognosis.

Poorly Cohesive Carcinoma of the Nonampullary Small Bowel: A Rare Cause of Recurrent Small Bowel Obstruction.

Poorly cohesive carcinoma (PCC) is an uncommon neoplasm characterized by tumorous cells exhibiting a lack of adhesion. PCC has been reported rarely in the small intestine other than at the ampulla of Vater. We present a 40-year-old man with recurrent abdominal pain and small bowel obstruction. Imaging revealed an abnormal appearing distal small bowel, with only nonspecific mucosal changes discovered on antegrade and retrograde enteroscopy. On subsequent diagnostic laparoscopy, an ileal mass was found and resected with histopathology showing PCC with signet ring formation. This is an aggressive cancer with a worse prognosis than other small bowel adenocarcinomas.

Expression of claudin 18.2 in poorly cohesive carcinoma and its association with clinicopathologic parameters in East Asian patients.

BACKGROUND: Poorly cohesive carcinoma (PCC) is a distinct subtype of gastric cancer with limited therapeutic options. This study investigated claudin (CLDN) 18.2 expression status in PCCs using a 43-13 A clone. METHODS: We retrospectively collected 178 consecutive surgically resected stage Ⅱ-Ⅲ gastric cancer samples. Tissue microarray blocks were constructed for CLDN18.2 immunohistochemical staining. We studied CLDN18.2 expression and its association with clinicopathologic parameters. RESULTS: CLDN18.2 positivity (defined by ≥ 75 % of tumor cells showing moderate to strong membranous positivity) was found in 34.8 % of the PCC cases (62/178). Approximately half of the CLDN18.2 positive PCCs demonstrated heterogeneous expression (51.6 %, 32/62). CLDN18.2 positivity was not associated with any clinicopathologic parameters examined. However, CLDN18.2 positivity tended to be more frequent in E-cadherin-positive PCCs (no loss of expression) than in E-cadherin-negative PCCs (loss of expression) (50 % vs. 27.7 %). The CLDN18.2 expression level, represented by the H-score, gradually decreased as the paraffin block storage time increased (P = 0.046). Overall survival and disease-free survival analyses showed no significant difference between CLDN18.2-positive and negative PCCs. CONCLUSIONS: A significant portion of surgically resected PCC specimens showed CLDN18.2 positivity. Additionally, since the expression level of CLDN18.2 gradually decreases with increased paraffin block storage time, reflex testing can be considered at the time of the cancer diagnosis.

Clinicopathological features and cancer transcriptomic profiling of poorly cohesive gastric carcinoma subtypes.

Gastric poorly cohesive carcinoma (PCC) manifests with a diffuse pattern and diverse tumor cell morphologies, often indicating a more unfavorable prognosis. Recent consensus has reclassified PCC based on the proportion of signet-ring cells (SRCs) in tumors for research purposes. The two most distinct subtypes, poorly cohesive carcinoma not otherwise specified (PCC-NOS) and signet-ring cell carcinoma (SRCC), are characterized by less than 10% and more than 90% SRCs, respectively. However, research comparing the clinicopathological and transcriptomic differences between these subtypes remains limited. In this study, we conducted a comparative analysis of clinicopathological features in 55 advanced-stage PCCs, consisting of 43 PCC-NOS and 12 SRCC cases. Subsequently, 12 PCC-NOS and 5 SRCC cases were randomly selected for initial cancer-related gene expression profiling and pathway enrichment analysis using the GeoMx digital spatial profiler, followed by validation in a separate validation group comprising 16 PCC-NOS and 6 SRCC cases. These transcriptomic findings were then correlated with tumor morphology and clinicopathological data. PCC-NOS cases exhibited larger tumor size, a higher prevalence of pathological N3 disease, and a worse 1-year progression-free survival rate compared to SRCC cases. Clustering of PCC-NOS and SRCC was successfully achieved using the GeoMx Cancer Transcriptome Atlas. Among all studied genes, only MMP7 showed differential expression, with its overexpression significantly associated with the PCC-NOS subtype, increased perineural invasion, and earlier disease progression. Pathway analysis revealed significantly enriched pathways in PCC-NOS related to vesicle-mediated transport, adaptive immune systems, oncogenic signaling, and extracellular matrix organization, while SRCC displayed significant enrichment in pathways associated with respiratory electron transport and the cell cycle. In conclusion, this study compares and correlates clinicopathological features and transcriptomic data between PCC-NOS and SRCC at advanced stages, employing the latest consensus classification and a novel platform for analysis.

Prognostic Survival Significance of Signet Ring Cell (SRC) Gastric Cancer: Retrospective Analysis from a Single Western Center.

INTRODUCTION: Signet ring cell carcinoma accounts for 35% to 45% of all gastric cancer. Despite the acknowledgment of its more aggressive pathological features, various controversies surrounding this topic still exist. Thus, we investigate the clinical pathological characteristics and survival prognostic significance of signet ring cell components in patients affected by gastric cancer. METHODS: From January 2004 to December 2020, in a retrospective study, we enrolled 404 patients with gastric cancer who were curatively treated in our department. The male-to-female ratio was 249/142, and the median age was 75 (range 37-94). We dichotomized patients into two groups (75 patients vs. 316 patients) based on the signet ring cell presence; according to preoperative, operative, and postoperative characteristics, we performed a univariate and multivariate analysis for overall survival. RESULTS: Signet ring cell carcinoma indicated an increasing incidence trend over the time analyzed. Overall median survival of signet ring cell and non-signet ring cell carcinoma were, respectively, 16 vs. 35 months, p < 0.05. In early gastric cancer, the prognosis of the signet ring cell is better than that of the non-signet ring cell, as opposed to advanced cancer. Among the entire population in the multivariate analysis, the only independent factors were preoperative serum albumin level, complete surgical resection, level of lymphadenectomy, and pathological stage. Recurrence occurred more frequently in patients affected by signet ring cell, but in our data, we could not identify a peculiar site of recurrence. CONCLUSIONS: Signet ring cell carcinoma has a specific oncogenetic phenotype and treatment resistance heterogeneity; however, it is not always associated with poor prognosis. According to our results, a radical surgical procedure associated with an adequate lymphadenectomy should be advocated to improve patients survival. Gastric cancer patients with signet ring cell components should draw clinicians' attention.

Poorly cohesive duodenal carcinoma mixed with signet ring cell carcinoma with systemic metastasis: a case report and literature review.

Poorly cohesive duodenal carcinoma mixed with signet ring cell carcinoma is very rare, and no cases have been reported. When distant metastasis occurs, it is very easy to be misdiagnosed. We report the first case of a 52-year-old man with poorly cohesive carcinoma of the duodenum mixed with signet ring cell carcinoma with systemic metastasis. The process of its diagnosis and differential diagnosis is highlighted.

Comparison of Gene Expression Profiles of Signet Ring Cell Carcinoma and Poorly Cohesive Carcinoma in Early Gastric Cancer.

Introduction: Although signet ring cell carcinoma (SRC) is a subtype of poorly cohesive carcinoma (PC), the differences in the biological behavior between the 2 morphologically similar carcinomas have not been fully studied. Therefore, we performed transcriptome analysis to evaluate the differences of genetic expressions between SRC and PC. Methods: The study group consisted of patients with SRC or PC pathology from patients with early gastric cancer (EGC) whose depth of invasion was localized in the mucosal layer. A total of 18 patients were enrolled. The patients were divided into 3 groups based on their histologic type and lymph node (LN) status. Group 1 consisted of patients with PC and positive LN metastasis, Group 2 consisted of patients with PC without LN metastasis, and Group 3 consisted of patients with SRC without LN metastasis. Transcriptome analysis was performed using the nCounter PanCancer Progression Panel Kit. Results: The expression of 77 genes in Group 1 was altered compared to that in normal tissues. The expression of 49 and 13 genes in Groups 2 and 3, respectively, was altered when compared to that in normal tissues. Groups 1 and 2 showed similar genetic expressions. However, Group 3 showed numerous differences in gene expression including Roundabout4 (Robo4) compared to the other groups, especially Group 1. Conclusion: Our data suggest that gene expression patterns were different between SRC and PC and expression of ROBO4 may play an important role in the prognosis of SRC and PC type of EGC.

Metastatic Breast Lobular Carcinoma to Unusual Sites: A Report of Three Cases and Review of Literature.

Invasive lobular carcinoma of the breast is the second most common type of invasive breast carcinoma. Invasive lobular carcinoma has an unusual pattern of metastases, which poses a diagnostic challenge for both clinicians and pathologists. We herein present three cases of breast invasive lobular carcinoma presented with metastasis to unusual sites, namely, uterus, colon and stomach. We recommend a higher index of suspicion in any case with breast cancer developing gastrointestinal tract or genital tract symptoms.

Prognostic significance of poorly cohesive gastric carcinoma in Tunisian patients.

BACKGROUND: While the incidence of gastric cancer has decreased worldwide in recent decades, the incidence of poorly cohesive carcinoma (PCC) is rising. The prognostic significance of gastric PCC remains a subject of debate. OBJECTIVE: To analyze the prognosis of gastric PCC in a Tunisian cohort. METHODS: A total of 122 gastric adenocarcinoma patients who underwent curative gastrectomy from 2001 to 2014 at Habib Thameur hospital in Tunis, Tunisia were included. The clinicopathological parameters and prognosis of PCC were analyzed in comparison with non PCC (NPCC). RESULTS: Sixty one patients (50%) presented PCC. Patients were younger in PCC group (p = 0,001). There was no difference in sex distribution between the two groups. PCC was more likely to be stage T4 (55.7% vs 34.4%; p = 0.033), N3 (67.8% vs 30%; p < 0.001) and have a higher metastatic lymph node ratio (p < 0.001). Hepatic metastases were more frequent in NPCC group (p = 0.031) whereas peritoneal carcinomatosis was more common in PCC group (p = 0.004). Perineural invasion was more frequent in PCC group (p = 0.001). Resection margins were more often positive in PCC group (31.1% vs 9.8%; p = 0.004). There was no difference in recurrence rate between the 2 groups (p = 0.348). The 5-year survival was similar in the NPCC and PCC (respectively 43% vs 23 %; p = 0.247). Survival rates were also comparable in early stage (100% vs 80% respectively for PCC and NPCC; p = 0.527) as well as for advanced stage (16% vs 35% respectively for PCC and NPCC; p = 0.538). PCC was not a prognostic factor for survival. Interestingly, advanced age, adjacent structures invasion, positive resection margins were specific prognostic factors for PCC. CONCLUSION: In our study PCC was not a prognostic factor for survival. Advanced age, adjacent structures invasion and positive resection margins were specific prognostic features for this histological subtype.