Mapping the landscape of gastric signet ring cell carcinoma:Overcoming hurdles and charting new paths for advancement

BACKGROUND In recent years,the global prevalence of gastric cancer(GC)has witnessed a progressive decrease,accompanied by a step-growth in the incidence of gastric signet ring cell carcinoma(GSRCC).As precision medicine concepts progress,GSRCC,a distinct sub-type of GC,has drawn considerable attention from researchers.However,there still persist some controversies regarding the associated research findings.AIM To summarize the current obstacles and potential future directions for research on GSRCC.METHODS To begin with,all literature related to GSRCC published from January 1,2004 to December 31,2023 was subjected to bibliometric analysis in this article.Additionally,this paper analyzed the research data using CiteSpace,GraphPad Prism v8.0.2,and VOSviewer,which was obtained from the Web of Science Core Collection database.The analysis results were visually represented.RESULTS This study provided a comprehensive overview of the statistical characteristics of the 995 English articles related to GSRCC,including cited references,authors,journals,countries,institutions,and keywords.The popular keywords and clusters contain"prognosis","survival","expression","histology",and"chemotherapy".CONCLUSION The prognosis,precise definition and classification,as well as chemoresistance of GSRCC,continue to be crucial areas of ongoing research,whose directions are closely tied to advancements in molecular biology research on GSRCC.

Signet-ring cell carcinoma of the transverse colon in a 10-year-old girl:A case report

BACKGROUND Signet-ring cell carcinoma(SRCC)is a rare subtype of colorectal cancer.The incidence of primary colonic SRCC is relatively rare in pediatric patients,with a limited number of reported cases currently available.The prognosis for this specific tumor type is unfavorable,and the preoperative diagnosis presents challenges,potentially leading to misdiagnosis.This case report describes the diagnosis of primary SRCC in the colon of a 10-year-old girl.CASE SUMMARY The patient was admitted to the hospital due to abdominal pain and vomiting.A computed tomography scan revealed an irregular mass with soft tissue density in her transverse colon,showing uneven density and multiple calcifications.The patient underwent surgical resection of the affected bowel and lymph node dissection,which was confirmed by pathological examination to be SRCC infiltrating both nerves and the entire intestinal wall.Additionally,tumor thrombus formation was observed in blood vessels and lymphatic vessels,multiple cancerous nodules were found in the omentum,and metastasis to 18 of 26 mesenteric lymph nodes examined.Immunohistochemistry for mismatch repair gene protein demonstrated microsatellite stability.No mutations in KRAS,NRAS,BRAF,or PIK3CA genes were detected through molecular pathology analysis.After surgery,she received standard chemotherapy for 8 cycles without tumor progression or other abnormalities during a 12-month follow-up period CONCLUSION Primary colonic SRCC is a rare malignant tumor with atypical clinical symptoms,and timely identification and intervention are crucial for improving the prognosis.

Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma

BACKGROUND The Alcian blue(AB)and periodic acid Schiff(PAS)stains are representative mucus markers in gastric signet ring cell carcinoma(SRCC).They are low-cost special staining methods used to detect acidic mucus and neutral mucus,respectively.However,the clinical importance of the special combined AB and PAS stain is unclear.AIM To investigate AB expression,PAS expression and the AB-to-PAS(A/P)ratio in gastric SRCC patients and to assess patient prognosis.METHODS Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS,and signet ring cell positivity was assessed quantitatively.Immuno-histochemical staining for Ki67,protein 53(P53)and human epidermal growth factor receptor 2(HER2)was performed simultaneously.The cancer-specific survival(CSS)rate was estimated via Kaplan-Meier analysis.Cox proportional hazards models were used for univariate and multivariate survival analyses.RESULTS Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup(P<0.001).The 3-year CSS rate in the A/P≤0.5 group was significantly greater than that in the A/P>0.5 group(P=0.042).Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter,lymph node metastasis,vessel carcinoma embolus,tumor stage,the A/P ratio and the expression of Ki67,P53 and the PAS.Cox multivariate regression analysis confirmed that low PAS expression[hazard ratio(HR)=3.809,95%confidence interval(CI):1.563-9.283,P=0.003]and large tumor diameter(HR=2.761,95%CI:1.086-7.020,P=0.033)were independent risk factors for poor prognosis.CONCLUSION A/P>0.5 is potentially a risk factor for prognosis,and low PAS expression is an independent risk factor in the prognosis of gastric SRCC.PAS expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.

Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma:A population-based study

BACKGROUND Gastric signet ring cell carcinoma(GSRC)represents a specific subtype of gastric cancer renowned for its contentious epidemiological features,treatment principles,and prognostic factors.AIM To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC(LAGSRC)after surgery.METHODS The annual rates of GSRC incidence and mortality,covering the years 1975 to 2019,were extracted from the Surveillance,Epidemiology,and End Results(SEER)database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software.The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates.The Cox regression model was used to explore the independent prognostic factors for overall survival(OS).The risk factors extracted were used to establish a prognostic nomogram.RESULTS The overall incidence of GSRC increased dramatically between 1975 and 1998,followed by a significant downward trend in incidence after 1998.In recent years,there has been a similarly optimistic trend in GSRC mortality rates.The trend in GSRC showed discrepancies based on age and sex.Receiver operating characteristic curves,calibration curves,and decision curve analysis for 1-year,3-year,and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram.The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system.CONCLUSION The model we established can aid clinicians in the early prognostication of LAGSRC patients,resulting in improved clinical outcomes by modifying management strategies and patient health care.

Gastroesophageal signet ring cell carcinoma morbidity and mortality: A retrospective review

BACKGROUND Upper gastrointestinal(GI)signet ring cell carcinomas(SRCC)confer a poor prognosis.The benefit of operative intervention for this patient group is contro-versial in terms of overall survival.AIM To investigate factors relating to survival in patients with upper GI SRCC.METHODS A retrospective,tertiary,single-centre review of patients who were diagnosed with oesophageal,gastroesophageal junction and gastric SRCC was performed.The primary outcome was to compare mortality of patients who underwent operative management with those who had nonoperative management.Secon-dary outcomes included assessing the relationship between demographic and histopathological factors,and survival.RESULTS One hundred and thirty-one patients were included.The one-year survival for the operative group was 81%and for the nonoperative group was 19.1%.The five-year survival in the operative group was 28.6%vs 1.5%in the nonoperative group.The difference in overall survival between groups was statistically significant(HR 0.19,95%CI(0.13-0.30),P<0.001).There was no difference in survival when ad-justing for age,smoking status or gender.On multivariate analysis,patients who underwent surgical management,those with a lower stage of disease,and those with a lower Charlson Comorbidity Index(CCI)had significantly improved sur-vival.CONCLUSION Well-selected patients with upper GI SRCC appear to have reasonable medium-term survival following surgery.Offering surgery to a carefully selected patient group may improve the outcome for this disease.

Signet-ring cell carcinoma of the stomach: Impact on prognosis and specific therapeutic challenge

While the incidence of gastric cancer has decreased worldwide in recent decades,the incidence of signetring cell carcinoma(SRCC) is rising. SRCC has a specific epidemiology and oncogenesis and has two forms: early gastric cancer,which can be resected endoscopically in some cases and which has a better outcome than non-SRCC,and advanced gastric cancer,which is generally thought to have a worse prognosis and lower chemosensitivity than non-SRCC. However,the prognosis of SRCC and its chemosensitivity with specific regimens are still controversial as SRCC is not specifically identified in most studies and its poor prognosis may be due to its more advanced stage. It therefore remains unclear if a specific therapeutic strategy is justified,as the benefit of perioperative chemotherapy and the value of taxanebased chemotherapy are unclear. In this review we analyze recent data on the epidemiology,oncogenesis,prognosis and specific therapeutic strategies in both early and advanced SRCC of the stomach and in hereditary diffuse gastric cancer.

Signet-ring cell carcinoma arising from a fundic gland polyp in the stomach

Fundic gland polyps(FGPs)are currently the most common type of gastric polyps and are usually benign.However,although rare,gastric adenocarcinoma of FGP has been recently proposed as a new variant of gastric adenocarcinoma.Here we report the first case of a49-year-old woman with focal signet ring cell carcinoma that arose from an FGP of the stomach.The tumor was completely excised by endoscopic snare polypectomy.FGPs should therefore be evaluated for malignant changes although they occur rarely,if the FGP has an erosive or irregular surface.

Neoadjuvant chemotherapy vs upfront surgery for gastric signet ring cell carcinoma:A retrospective,propensity score-matched study

BACKGROUND The benefit of neoadjuvant chemotherapy for patients with signet-ring cell carcinoma of the stomach is controversial.AIM To evaluate the perioperative and long-term outcomes of neoadjuvant chemotherapy for locally advanced gastric signet-ring cell carcinoma.METHODS This retrospective study identified patients with locally advanced signet-ring cell carcinomas of the stomach(cT3/4 and cN any)diagnosed from January 2012 to December 2017 by using the clinical Tumor-Node-Metastasis(cTNM)staging system.We performed 1:1 propensity score matching(PSM)to reduce bias in patient selection.The histologic and prognostic effects of neoadjuvant chemotherapy were assessed.The overall survival rates were used as the outcome measure to compare the efficacy of neoadjuvant chemotherapy vs surgery-first treatment in the selected patients.RESULTS Of the 144 patients eligible for this study,36 received neoadjuvant chemotherapy,and 108 received initial surgery after diagnosis.After adjustment by PSM,36 pairs of patients were generated,and baseline characteristics,including age,sex,American Society of Anesthesiologists score,tumor location,and cTNM stage,were similar between the two groups.The R0 resection rates were 88.9%and 86.1%in the surgery-first and neoadjuvant chemotherapy groups after PSM,respectively(P=1.000).The median follow-up period was 46.4 mo.The 5-year overall survival rates of the neoadjuvant chemotherapy group and surgery-first group were 50.0%and 65.0%(P=0.235),respectively,before PSM and 50%and 64.7%(P=0.192),respectively,after PSM.Multivariate analyses conducted before and after PSM showed that NAC was not a prognostic factor.CONCLUSION Neoadjuvant chemotherapy provides no survival benefit in patients with locally advanced gastric signet-ring cell carcinoma.For resectable gastric signet-ring cell carcinoma,upfront surgery should be the primary therapy.

Phenotypic classification of gastric signet ring cell carcinoma and its relationship with clinicopathologic parameters and prognosis

AIM: To distinguish subtypes of gastric signet ring cell (SRC) carcinoma by investigating the expression of gastric and intestinal phenotypic markers, and to study the significance of phenotypic classification in predicting tumor progression and outcome. METHODS: Immunohistochemistry was performed in 66 cases of SRC carcinoma with MUC2, VILLIN, CDX2, Li-cadherin antibodies as intestinal phenotype markers and MUC5AC, HGM, MUC6 antibodies as gastric phenotype markers, and the relationship was analyzed between the phenotypic expression pattern and clinicopathologic parameters, as well as the 3-year survival rate. RESULTS: Expression of intestinal phenotypic markers was positively associated with tumor size, wall invasion, vascular invasion, lymph node metastasis and tumor-node-metastasis (TNM) stage. Cases expressing one or more intestinal markers had a significant lower survival rate than cases expressing none of the intestinal markers. CONCLUSION: The SRC carcinomas expressing intestinal phenotype markers exhibited a high pro-liferative potential, bad biological behaviors and poor prognosis. Examination of phenotype expression may be useful in distinguishing histological type and in predicting the prognosis of gastric SRC carcinoma.

Gastric adenocarcinoma of fundic gland type with signet-ring cell carcinoma component: A case report and review of the literature

A depressed lesion was found at a gastric angle of 76-yearold Japanese woman by esophagogastroduodenoscopy. Four years prior, she was diagnosed with a Helicobacter pylori infection but no eradication was performed. The pathological diagnosis of biopsy specimens was signet-ring cell carcinoma. Endoscopic submucosal dissection(ESD) was performed. Histopathological examination of the ESD specimen revealed proliferation of well-differentiated tubular adenocarcinoma mimicking fundic gland cells at the deep layer of the lamina propria mucosae. These tumor cells expressed focally pepsinogen-Ⅰ, diffusely MUC6, and scattered H^+/K^+ ATPase according to immunohistochemistry. Therefore, we diagnosed this tumor as gastric adenocarcinoma of fundic gland type(GA-FG). Adjacent to the GA-FG, proliferation of signet-ring cell carcinoma which diffusely expressed MUC 2 and MUC 5AC was observed. Intestinal metaplasia was focally observed in the surrounding mucosa of the signet-ring cell carcinoma. To the best of our knowledge, this is the first case report of GA-FG with a signet-ring cell carcinoma component. The origin of signet-ring cell carcinoma, i.e., whether it accidentally arose from a non-neoplastic mucosa and coexisted with the GA-FG or dedifferentiated from the GA-FG is unclear at present. We expect the accumulation of similar cases and further analysis to clarify this issue.

Early-stage primary signet ring cell carcinoma of the colon

Primary signet ring cell carcinoma of the colorectum detected at an early stage is very rare; most cases are detected at an advanced stage. Therefore, its progno-sis is poorer than that of ordinary colorectal cancer. A 56-year-old Korean man was seen at this hospital for management of signet ring cell carcinoma of the co-lon. Colonoscopic examination revealed a Ⅱa-like, ill-defined and flatly elevated 9-mm residual tumor in the cecum. Endoscopic mucosal resection was preformed. Pathological examination of the resected specimen re-vealed signet ring cell carcinoma that had invaded the lamina propria without venous or perineural invasion. Abdominal computed tomography (CT) and positron CT showed no evidence of primary lesions or distant me-tastasis. An additional laparoscopic right-hemicolectomy was performed; no residual tumor or lymph node me-tastasis was found. We report a case of primary signet ring cell carcinoma of the colon detected at an early stage and provide a review of the literature.

Diagnosis of small intramucosal signet ring cell carcinoma of the stomach by non-magnifying narrow-band imaging: A pilot study

AIM: To examine the efficacy of non-magnifying narrow-band imaging(NM-NBI) imaging for small signet ring cell carcinoma(SRC).METHODS: We retrospectively analyzed 14 consecutive small intramucosal SRCs that had been treated with endoscopic submucosal dissection(ESD) and 14 randomly selected whitish gastric ulcer scars(control). The strength and shape of the SRCs and whitish scars by NM-NBI and white-light imaging(WLI) were assessed with Image J(NIH, Bethesda).RESULTS: NM-NBI findings of SRC showed a clearly isolated whitish area amid the brown color of the surrounding normal mucosa. The NBI index, which indicates the potency of NBI for visualizing SRC, was significantly higher than the WLI index(P = 0.001), indicating SRC was more clearly identified by NM-NBI. Although the NBI index was not significantly different between SRCs and controls, the circle(C)-index, as an index of circularity of tumor shape, was significantly higher in SRCs(P = 0.001). According to the receiveroperating characteristic analysis, the resulting cut-off value of the circularity index(C-index) for SRC was 0.60(85.7% sensitivity, 85.7% specificity). Thus a lesion with a C-index ≥ 0.6 was significantly more likely to be an SRC than a gastric ulcer scar(OR = 36.0; 95%CI: 4.33-299.09; P = 0.0009).CONCLUSION: Small isolated whitish round area by NM-NBI endoscopy is a useful finding of SRCs which is the indication for ESD.

Primary signet ring cell carcinoma of the appendix:A rare case report and our 18-year experience

Primary adenocarcinoma of the appendix is a rare malignancy that constitutes 〈 0.5% of all gastrointestinal neoplasms. Moreover, primary signet ring cell carc noma of the appendix is an exceedingly rare entity. We have encountered 15 cases of primary appendiceal cancer among 3389 patients who underwent appen- dectomy over the past 18 years. In the present report, we describe a rare case of primary signet ring cell carcinoma of the appendix with ovarian metastases and unresectable peritoneal dissemination occurring in a 67-year-old female patient. She underwent ap- pendectomy and bilateral salpingo-oophorectomy with a laparoscopy procedure. She then received palliative systemic chemotherapy with 12 cycles of oxaliplatin, 5-flurorouracil, and leucovorin （FOIFOX-4）. The patient currently is well without progression of disease 12 mo after beginning chemotherapy.

BRAF mutation in colorectal carcinomas with signet ring cell component

Objective:Signet ring cell carcinoma is a rare subtype of colorectal carcinoma(CRC)with an associated BRAFV600E mutation.We investigated frequencies of BRAF mutation in 28 CRCs containing variable signet ring cell component and their relation with clinicopathologic parameters.Methods:According to the presence of signet ring cell component,tumors were categorized into groups as follows:0%–9%,10%–24%,25%–49%,and>50%.Genomic DNA was isolated and analyzed for BRAF V600E gene mutation by polymerase chain reaction-restriction fragment length polymorphism.Eleven of 28 cases(39.3%)showed BRAFV600E mutation,which was also confirmed by Sanger sequencing.To elucidate the importance of existence of signet ring cell component at the molecular level,we separated cases into two groups with cut-off levels of 10%and 50%,which pertain to percentages of signet ring cells.Results:Seven of 19 cases(36.8%)under the threshold of 50%and four of nine cases(44.4%)over this threshold value demonstrated BRAF mutation.Three of 7 cases(42.8%)featuring<10%signet ring cell component and eight out of 21 cases(38.1%)showing>10%were BRAF mutated.Conclusions:BRAF mutation must be closely associated with the presence of malignant signet ring cells regardless of their percentages.

Endoscopic features of early-stage signet-ring-cell carcinoma of the stomach

AIM: To identify the features of early signet ring cell gastric carcinoma using magnification endoscopy with narrow band imaging(NBI).METHODS: A retrospective review was conducted of 12 cases of early signet ring cell gastric carcinoma who underwent treatment in a single institution between January 2009 and April 2013. All patients had magnification endoscopy with NBI and indigo carmine contrast to closely examine the mucosal architecture, including the microvasculature and arrangement of gastric pits. Histologic examination of the final endoscopic submucosal dissection or gastrectomy specimen was performed and compared with the endoscopic findings to identify patterns specific to signet ring cell carcinoma.RESULTS: Twelve patients with early signet ring cell gastric carcinoma were identified; 75% were male, and average age was 61 years. Most of the lesions were stage T1a(83%), while the remainder were T1b(17%). The mean lesion size was 1.4 cm2. On standard endoscopy, all 12 patients had a pale, flat lesion without any evidence of mucosal abnormality such as ulceration, elevation, or depression. On magnification endoscopywith NBI, all of the patients had irregularities in the glands and microvasculature consistent with early gastric cancer. In addition, all 12 patients exhibited the "stretch sign", an elongation or expansion of the architectural structure. Histologic examination of the resected specimens demonstrated an expanded and edematous mucosal layer infiltrated with tumor cells.CONCLUSION: The "stretch sign" appears to be specific for signet ring cell carcinoma and may aid in the early diagnosis and treatment of this aggressive pathology.

Primary signet ring cell carcinoma of the appendix: A rare case report

Primary adenocarcinoma of the appendix is a rare malignancythat constitutes < 0.5% of all gastroin-testinalneoplasms. Moreover, primary signet ring cell carcinomaof the appendix is an exceedingly rare entity. In the present report, we describe a rare case of primary signet ring cell carcinoma of the appendix with ovarian metastasesand unresectable peritoneal dissemination occurring in a 45-year-old female patient. She was clinically misdiagnosed as torsion of ovarian cyst. She underwent appendicectomy and unilateral salpingooophorectomy.Histopathology revealed signet ring cell carcinoma and a right hemicolectomy was done. She then received palliative systemic chemotherapy with 12 cycles of oxaliplatin, 5-fluorouracil, and leucovorin(FOLFOX-4). The patient is doing well till today on follow up without progression of disease 10 mo after beginning chemotherapy.

Signet ring colorectal carcinoma:Do we need to improve the treatment algorithm?

AIMTo elaborate about this peculiar variant from a tertiary cancer center from India. METHODSIt&rsquo;s a retrospective study (2011-2014) of all patients diagnosed with signet ring colo-rectal cancer (SRCC). Various clinico-pathological variables were studied. RESULTSOne hundred and seventy consecutive patients with SRCC were diagnosed (11.4% of all colorectal cancers). Median Age of the cohort was 41 years. Most common location was recto-sigmoid area (54.7%). Majority patients presented in stage III and IV (91.2%). Most of the stage IV patients had isolated peritoneal metastases (86.5%). Colonic tumors had higher incidence of peritoneal metastases (91.8% vs 83.3%) as well as isolated peritoneal recurrences (37.5% vs 16.7%) than rectal primaries. Thirty-seven point five percent of patients recurred after curative surgery. Amongst them 63.63% patients had isolated peritoneal recurrences. Circumferential resection margin (CRM) was involved in 17.9% patients. Median relapse free survival (RFS) and overall survival (OS) of the cohort were 14.9 and 18.13 mo respectively. CRM involvement, colonic primary were associated with poorer RFS and OS. CONCLUSIONSRCC has predilection for peritoneal dissemination. More aggressive and/or extended chemotherapy schedules as well as prophylactic hyperthermic intra-peritoneal chemotherapy at the time of primary surgery may be attempted in these patients.

Minute signet ring cell carcinoma occurring in gastric hyperplastic polyp

We describe a 45-year-old woman with minute signet ring cell carcinoma occurring in a gastric hyperplastic polyp. A biopsy specimen obtained from the gastric hyperplastic polyp revealed signet ring cell carcinoma. Endoscopic mucosal resection (EMR) was performed to confirm the diagnosis. Histological examination of the EMR specimen revealed focal signet ring cell carcinoma in the hyperplastic polyp. There are few cases of gastric hyperplastic polyp associated with signet ring cell carcinoma.

Development and validation of prognostic nomogram based on log odds of positive lymph nodes for patients with gastric signet ring cell carcinoma

Objective: Our aims were to establish novel nomogram models, which directly targeted patients with signet ring cell carcinoma(SRC), for individualized prediction of overall survival(OS) rate and cancer-specific survival(CSS).Methods: We selected 1,365 SRC patients diagnosed from 2010 to 2015 from Surveillance, Epidemiology and End Results(SEER) database, and then randomly partitioned them into a training cohort and a validation cohort.Independent predicted indicators, which were identified by using univariate testing and multivariate analyses, were used to construct our prognostic nomogram models. Three methods, Harrell concordance index(C-index), receiver operating characteristics(ROC) curve and calibration curve, were used to assess the ability of discrimination and predictive accuracy. Integrated discrimination improvement(IDI), net reclassification improvement(NRI) and decision curve analysis(DCA) were used to assess clinical utility of our nomogram models.Results: Six independent predicted indicators, age, race, log odds of positive lymph nodes(LODDS), T stage, M stage and tumor size, were associated with OS rate. Nevertheless, only five independent predicted indicators were associated with CSS except race. The developed nomograms based on those independent predicted factors showed reliable discrimination. C-index of our nomogram for OS and CSS was 0.760 and 0.763, which were higher than American Joint Committee on Cancer(AJCC) 8 th edition tumor-node-metastasis(TNM) staging system(0.734 and 0.741, respectively). C-index of validation cohort for OS was 0.757 and for CSS was 0.773. The calibration curves also performed good consistency. IDI, NRI and DCA showed the nomograms for both OS and CSS had a comparable clinical utility than the TNM staging system.Conclusions: The novel nomogram models based on LODDS provided satisfying predictive ability of SRC both in OS and CSS than AJCC 8 th edition TNM staging system alone.

Overexpression of the M2 isoform of pyruvate kinase is an adverse prognostic factor for signet ring cell gastric cancer

AIM:To investigate M2 isoform of pyruvate kinase(PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target.METHODS:All tissue samples were derived from gastric cancer patients underwent curative gastrectomy as a primary treatment.Clinical and pathological information were obtained from the medical records.Gene expression microarray data from 60 cancer and 19 noncancer gastric tissues were analyzed to evaluate the expression level of PKM2 mRNA.Tissue microarrays were constructed from 368 gastric cancer patients.Immunohistochemistry was used to measure PKM2 expression and PKM2 positivity of cancer was determined by proportion of PKM2-positive tumor cells and staining intensity.Association between PKM2 expression and the clinicopathological factors was evaluated and the correlation between PKM2 and cancer prognosis was evaluated.RESULTS:PKM2 mRNA levels were increased more than 2-fold in primary gastric cancers compared to adjacent normal tissues from the same patients(log transformed expression level:7.6 ± 0.65 vs 6.3 ± 0.51,P < 0.001).Moreover,differentiated type cancers had significantly higher PKM2 mRNA compared to undifferentiated type cancers(log transformed expression level:7.8 ± 0.70 vs 6.7 ± 0.71,P < 0.001).PKM2 protein was mainly localized in the cytoplasm of primary cancer cells and detected in 144 of 368(39.1%) human gastric cancer cases.PKM2 expression was not related with stage(P = 0.811),but strongly correlated with gastric cancer differentiation(P < 0.001).Differentiated type cancers expressed more PKM2 protein than did the undifferentiated ones.Well differentiated adenocarcinoma showed 63.6% PKM2-positive cells;in contrast,signet-ring cell cancers showed only 17.7% PKM2-positive cells.Importantly,PKM2 expression was correlated with shorter overall survival(P < 0.05) independent of stage only in signet-ring cell cancers.CONCLUSION:PKM2 expression might be an adverse prognostic factor for signet-ring cell carcinomas.Its function and potential as a prognostic marker should be further verified in gastric cancer.