Histopathologic vertical margin positivity in cold snare polypectomy and mucosal resection for sessile serrated lesions.

BACKGROUND AND AIMS: Data regarding the status of the vertical margin of sessile serrated lesions (SSLs) resected using cold snare polypectomy (CSP) are lacking, and whether a histopathologically positive vertical margin is related to recurrence remains unclear. Therefore, this preliminary study aimed to clarify the rates of positive or unassessable vertical and horizontal margins and the rate of muscularis mucosae resection in SSLs treated using CSP compared with those treated with EMR. METHODS: Histologic outcomes of patients treated with CSP or EMR for SSLs were evaluated in this single-center observational study. The primary outcome was the incidence of histopathologically positive vertical margins in CSP and EMR. Furthermore, the comparisons were adjusted for confounding factors using propensity score matching. RESULTS: Overall, 82 patients with SSLs were included in the CSP and EMR groups after matching. The incidence of positive histologic vertical margins in the CSP and EMR groups were 67.1% and 2.4%, respectively (P < .001). Regarding the evaluation of the presence of muscularis mucosae, 29.3% and 98.8% of patients in the CSP and EMR groups, respectively, had a complete muscularis mucosae resection (P < .001). CONCLUSIONS: A rigorous histopathologic evaluation revealed that for SSLs, CSP more frequently leads to positive vertical margins than EMR. (Clinical trial registration number: UMIN 000051569.).

Evaluation of the prognostic impact of pathologic tumor regression grade on patients with colorectal cancer after preoperative chemoradiotherapy.

BACKGROUND: The prognostic value of the pathological response to preoperative chemoradiotherapy (CRT) in rectal cancer (RC) remains unknown. OBJECTIVES: We aimed to assess the predictive value of the response to CRT that was derived from an evaluation of the histological findings (whole-section vs. representative-section sampling) and attempted to determine an objective cut-off value for the tumor regression grade (TRG). METHODS: We examined the association of the TRG with the outcomes (recurrence-free survival [RFS] and overall survival [OS]) of 78 patients with RC. Patients with RC treated with preoperative CRT were divided into development (30 cases) and validation (48 cases) cohorts. The TRG was classified as grades I (Ia, Ib), II, and III. The cut-off value was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: The TRG determined from whole-section sampling versus representative-section sampling was more strongly correlated with patient survival. We found that in both cohorts, patients with a cut-off value of <73% had a poor prognosis. Finally, the cut-off value was found to be an independent predictive factor in both univariate and multivariate analysis. CONCLUSIONS: The TRG that was used to evaluate patients with RC who underwent preoperative CRT was an independent prognostic factor for outcome.

Differential Expression in the Tumor Microenvironment of mRNAs Closely Associated with Colorectal Cancer Metastasis.

BACKGROUND: Metastasis of colorectal cancer (CRC) is a major cause of CRC-related mortality. However, the detailed molecular mechanism of CRC metastasis remains unknown. A recent study showed that the tumor microenvironment, which includes cancer cells and the surrounding stromal cells, plays a major role in tumor invasion and metastasis. Identification of altered messenger RNA (mRNA) expression in the tumor microenvironment is essential to elucidation of the mechanisms responsible for tumor progression. This study investigated the mRNA expression of genes closely associated with metastatic CRC compared with non-metastatic CRC. METHODS: The samples examined were divided into cancer tissue and isolated cancer stromal tissue. The study examined altered mRNA expression in the cancer tissues using The Cancer Genome Atlas (TCGA) (377cases) and in 17 stromal tissues obtained from our laboratory via stromal isolation using an array-based analysis. In addition, 259 patients with CRC were enrolled to identify the association of the candidate markers identified with the prognosis of patients with stage 2 or 3 CRC. The study examined the enriched pathways identified by gene set enrichment analysis (GSEA) based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) module in both the TCGA dataset and isolated stromal tissue. RESULTS: As a result, whereas tenascin-C, secreted phosphoprotein 1 and laminin were expressed in metastatic CRC cells, olfactory receptors (ORs) 11H1 and OR11H4 were expressed in stromal tissue cells isolated from metastatic CRC cases. Finally, upregulated expression of tenascin-C and OR11H4 was correlated with the outcome for CRC patients. CONCLUSION: The authors suggest that upregulated expression levels of tenascin-C and OR11H1 play an important role in CRC progression.

The new IASLC grading system for invasive non-mucinous lung adenocarcinoma is a more useful indicator of patient survival compared with previous grading systems.

BACKGROUND: The International Association for the Study of Lung Cancer (IASLC) Pathology Committee recently proposed a new histological grading system for invasive lung adenocarcinoma (ADC). This study evaluated the usefulness of this grading system. METHODS: A total of 395 patients with ADC were examined. ADCs were reclassified based on comprehensive histological subtyping according to the IASLC grading system. We evaluated the following histological grading systems for invasive ADC: the architectural (Arch), Sica's grading, and IASLC grading systems. Multivariate analyses of overall and recurrence-free survival (RFS) based on these three grading systems were performed using Cox proportional hazards models. RESULTS: Multivariate analysis showed that all three grading systems were useful for predicting the outcomes of patients at all stages. However, the IASLC grading system was superior to the Arch and Sica's grading systems in differentiating grade 3 from grade 1 ADCs in terms of both overall survivals (IASLC vs. Arch vs. Sica's grading systems: hazard ratio [HR] = 3.77 vs. 3.03 vs. 2.63) and RFS (HR = 4.25 vs. 2.69 vs. 2.4). CONCLUSION: The newly proposed IASLC grading system was useful for predicting patient outcomes and was superior to the other grading systems in detecting high-grade malignancy.

Cribriform-type adenocarcinoma of the colorectum: comprehensive molecular analyses of a distinctive histologic subtype of colorectal cancer.

Colorectal adenocarcinoma (CRA) is characterized by marked heterogeneity and may be composed of an admixture of various histologic patterns, including well-formed gland and cribriform types. Although tumors displaying a prominent or predominant cribriform feature are frequently found in CRA, this type may contain specific histologic variants with a characteristic molecular alteration. We investigated the molecular features of 51 primary CRAs with a predominant cribriform histology using array-based analyses [somatic copy number alterations (SCNAs); mRNA expression]. Mutations (TP53, KRAS, PIK3CA and BRAF) and DNA methylation status were also analyzed. The crypt isolation method was used to obtain isolated tumor glands of each type separately. All patients were classified by their CRA histologic subtype into two groups: well-formed gland and cribriform. Next, we performed cluster analysis to stratify SCNA and mRNA expression patterns between the two subtypes. Two distinctive subgroups were stratified based on patterns of SCNA and mRNA expression and were correlated with each histologic subtype. The cribriform type was characterized by a high frequency of SCNA compared with that of the well-formed gland type and was closely associated with the expression of specific mRNAs. In addition, the frequency of KRAS mutation was significantly higher in the cribriform type than in the well-formed gland type. Finally, there was no difference in DNA methylation status between the two subtypes. Overall, these data suggest that the cribriform type provides important insights into colorectal carcinogenesis, suggesting specific potential histologic implications based on the molecular profile.

Clinicopathological and molecular analyses of hyperplastic lesions including microvesicular variant and goblet cell rich variant hyperplastic polyps and hyperplastic nodules-Hyperplastic nodule is an independent histological entity.

Hyperplastic nodules (HNs) have been considered to be hyperplastic lesions among Japanese pathologists, although they have not been recognized worldwide. Here, we examined clinicopathological and molecular differences between goblet cell-rich variant hyperplastic polyp (GCHPs), microvesicular variant HPs (MVHPs), and HNs. Patients with hyperplastic lesions including 61 GCHPs, 62 MVHPs, and 19 HNs were enrolled in the present study. The clinicopathological and molecular features examined included the mucin phenotype expression, p53 overexpression, annexin A10, genetic mutations (BRAF and KRAS), and DNA methylation status (low, intermediate, and high methylation epigenotype). In addition, hierarchical cluster analysis was also performed to identify patterns among the histological features. The lesions were stratified into three subgroups and each lesion was assigned into a subgroup. While GCHP was associated with KRAS mutation, MVHP was closely associated with BRAF mutation; no mutation was found in HN. We list specific histological findings that corresponded to each lesion. Finally, there were no significant differences in the methylation status among lesions. The current result shows that both MVHPs and GCHPs have a neoplastic nature whereas HN is non-neoplastic. We suggest that HNs should be distinguished from HPs, in particular GCHPs, in terms of pathological and genetic features.

An autopsy case of hyperimmunoglobulin E syndrome with coronary fibrinoid necrotizing arteritis and an aneurysm.

We report a case of hyperimmunoglobulin (Ig) E syndrome (HIES) with a coronary artery aneurysm (CAA) in a 25-year-old Japanese man. He died suddenly due to chronic heart failure associated with HIES. We noted a CAA at the trunk of the left coronary artery and granulomatous and fibrinoid necrotizing arteritis of the middle portion of the left anterior descending during the autopsy. We speculate herein on the relationship between the aneurysm and arteritis. These findings facilitate a better understanding of the pathogenesis underlying HIES.

Microenvironmental markers are correlated with lymph node metastasis in invasive submucosal colorectal cancer.

AIMS: Recent studies have shown that the microenvironment can include cancer cells and cancer-associated fibroblasts (CAFs), and that both play important roles in the progression and metastasis of CRC. Here, we aimed to analyse the expression patterns of cancer cell- and CAF-related proteins in submucosal invasive colorectal cancer (SiCRC) and whether such markers are correlated with lymph node metastasis (LNM). METHODS AND RESULTS: Quantitative analysis was conducted for Ki-67, p53, ß-catenin and matrix metalloproteinase-7 (MMP7) to assess cancer cell markers. In addition, we examined CAF markers, including smooth muscle alpha-actin (α-SMA), CD10, podoplanin, fibroblast-specific protein 1 (FSP-1), platelet-derived growth factor receptor (PDGFR)-α, PDGFR-ß, adipocyte enhancer-binding protein 1 (AEBP1), fibroblast-associated protein 1 (FAP-1), zinc finger E-box binding homeobox 1 (ZEB1) and TWIST-related protein 1 (TWIST1). In both cases, we conducted digital pathology with Aperio software. We also examined the expression patterns of biomarkers using hierarchical cluster analysis. Two subgroups were established based on the expression patterns of cancer cell- and CAF- related markers, and the associations of these subgroups with clinicopathological variables. In multivariate analysis, subgroup 2, which was characterised by high expression of Ki-67, p53, FAP-1, platelet-derived growth factor receptor (PDGFR)-α, PDGFR-ß and TWIST1, was correlated with LNM (P < 0.01). Next, we examined the associations of individual biomarkers with LNM. Multivariate analysis showed that high expression levels of Ki-67 and FAP-1 were significantly associated with LNM (P < 0.05). CONCLUSIONS: Our findings showed that expression patterns of cancer cell- and CAF-related proteins may allow for stratification of patients into risk categories for LNM in SiCRC. In addition, Ki-67- and FAP-1-expressing microenvironmental cells might be helpful for identification of correlations with LNM in SiCRC.

Protective effect of proton pump inhibitors and potassium competitive acid blockers against post-gastric endoscopic submucosal dissection bleeding: a single-center, propensity score-matched analysis.

OBJECTIVES: Both potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) are known to be protective against bleeding after gastric endoscopic dissection (ESD) for early gastric cancers. The aim was to compare the effect of PPI and P-CAB treatment against bleeding after gastric ESD. MATERIALS AND METHODS: This was a single-center, retrospective analysis. Among 541 patients who underwent gastric ESD during the period from 2014 to 2019, we recruited subjects who were treated with PPIs (intravenous lansoprazole followed by oral esomeprazole) or a P-CAB before and after ESD. The incidence of post-ESD bleeding was compared between treatment groups. The risks associated with post-ESD bleeding were examined by univariate and multivariate analyses after propensity score-matching. RESULTS: The overall incidence of post-ESD bleeding was not significantly different between patients treated with PPIs (n = 362) and those treated with a P-CAB (n = 156) (3.0% vs 2.6%, respectively; p = .77). Even after propensity score matching (n = 153 in each group), the incidence was not significantly different between groups (2.6% vs 2.6%, respectively; p = 1.00). A multivariate analysis revealed that antithrombotic therapy (OR 4.85, 95% CI 1.14-20.57) was an independent factor associated with post-ESD bleeding. CONCLUSIONS: The incidence of post gastric ESD bleeding is not different between patients treated with PPI and patients treated with P-CAB. Antithrombotic therapy is an independent risk factor associated with post-ESD bleeding.

Prognostic nutritional index is an independent prognostic factor for older patients aged ≥ 85 years treated by gastric endoscopic submucosal dissection.

BACKGROUND: Clinical outcomes and prognostic factors for survival after endoscopic submucosal dissection (ESD) in older patients aged ≥ 85 years with early gastric cancer (EGC) are not well defined. The aim of this study was to investigate the clinical outcomes and prognostic factors for survival after ESD in older patients aged ≥ 85 years with EGC. METHODS: Clinical outcomes of 70 patients aged ≥ 85 years with EGC treated with ESD were evaluated retrospectively. Prognostic factors for overall survival (OS) were analyzed with the Kaplan-Meier method and a Cox proportional hazards model. RESULTS: During the follow-up period, 33 patients died from any cause, none of whom died from gastric cancer. OS probability after 3 years was 90.0%. Univariate analyses revealed that a neutrophil/lymphocyte ratio ≥ 2.6, a prognostic nutritional index (PNI) < 42.5 and low serum albumin value (< 3.5 g/dl) were associated with poor OS. Cox multivariate analysis revealed low PNI (< 42.5) to be an independent prognostic factor associated with OS (hazard ratio; 3.40, 95% confidence interval; 1.47-7.86, P = 0.004). CONCLUSIONS: PNI may be a useful parameter for making the decision to perform ESD for older patients aged ≥ 85 years with EGC.

Resectability of underwater endoscopic mucosal resection for duodenal tumor: A single-center, retrospective pilot study.

BACKGROUND AND AIM: Underwater endoscopic mucosal resection (U-EMR) has been attracting much attention as treatment for patients with nonampullary duodenal epithelial tumors (NADETs). We aim to compare treatment outcomes, including submucosal resectability, between patients undergoing U-EMR and conventional endoscopic mucosal resection (C-EMR) for NADET. METHODS: We conducted a retrospective review of 38 patients with NADET treated by U-EMR or C-EMR. In the resected specimens, we measured the horizontal length, the vertical distance from the muscularis mucosa to the margin at the deepest site, and the overall submucosal area. The submucosal index (SMI) was defined as the overall submucosal area divided by the largest horizontal length. These values and other treatment outcomes were compared between NADETs resected by U-EMR and C-EMR. RESULTS: The median size of lesions was 7 mm with a range of 3-13 mm. Although the incidence of adverse events and the rates of en bloc and R0 resection were not different in the two groups, the median procedure time was significantly shorter in the U-EMR group (11 min vs 13 min; P = 0.045). The median submucosal depth at the deepest site (1.22 mm vs 1.08 mm; P = 0.38) and the median SMI (0.44 vs 0.41; P = 0.42) were not different between groups. CONCLUSIONS: The resectability between NADETs treated by U-EMR and C-EMR was comparable. These results, together with the shorter procedure time required for U-EMR, suggest that U-EMR may have the potential to be the first choice for small to medium-sized NADET.

Clinicopathological and Molecular Findings of Differentiated-Type Minute Gastric Intramucosal Neoplasia.

BACKGROUND/AIMS: To evaluate gastric early differentiate-type carcinogenesis, we attempted to identify clinicopathological and biological differences in differentiated-type minute intramucosal neoplasia (MIMN), which was defined as a tumor with a diameter of < 5 mm. METHODS: We examined clinicopathological findings and biological factors, including TP53 overexpression, mucin phenotype, Ki-67-positive rate, MLH1, intranuclear accumulation of ß-catenin, and DNA methylation status (low methylation epigenotype [LME], intermediate methylation epigenotype, and high methylation epigenotype [HME]) in MIMNs. In addition, non-MIMNs were also analyzed. In the present study, MIMN and non-MIMN were also examined based on low-grade dysplasia, high-grade dysplasia, and intramucosal cancer (IMC). RESULTS: In clinicopathological findings, there were significant differences in sex ratios and tumor locations between MIMNs and non-MIMNs. Among the examined biological factors, no significant differences in the frequencies of biological factors were observed between the 2 intramucosal neoplasia types. However, the frequency of intranuclear accumulation of ß-catenin was higher in non-MIMNs than in MIMNs. Finally, although the frequency of HME was significantly lower in MIMNs than in non-MIMNs, the opposite was observed for LME. CONCLUSIONS: The current finding suggested that DNA methylation and accumulation of ß-catenin were closely associated with tumor development from MIMN to non-MIMN.

Risk Factors for Post-gastric Endoscopic Submucosal Dissection Bleeding with a Special Emphasis on Anticoagulant Therapy.

BACKGROUND: Little is known about the risk factors for post endoscopic submucosal dissection (post-ESD) bleeding with anticoagulant therapy. AIMS: We aimed to investigate the risk factors for post-ESD bleeding for early gastric cancer (EGC) with an emphasis on anticoagulant therapy. METHODS: We retrospectively analyzed 2355 EGCs, including 137 lesions in patients treated under anticoagulants. Clinicopathological findings were evaluated between lesions in patients with and without anticoagulant therapy with propensity score matching analysis. The factors associated with post-ESD bleeding were analyzed with multivariate analysis with a logistic regression method. RESULTS: After propensity score matching, post-ESD bleeding was significantly more frequent in lesions of patients with than without anticoagulant therapy (11.7% vs 1.5%, respectively; P = 0.001). A univariate analysis revealed that anticoagulant therapy, heparin bridge therapy, undifferentiated type, deep submucosal invasion, and resected specimen size were associated with post-ESD bleeding. A multivariate analysis revealed anticoagulant therapy (OR 23.1, 95% CI 3.61-147.52) and resected specimen size (OR 1.03, 95% CI 1.00-1.06) to be independent factors associated with post-ESD bleeding. CONCLUSIONS: Anticoagulant therapy and resected specimen size were risk factors associated with post-ESD bleeding for EGC.

Diagnostic algorithm of magnifying endoscopy with crystal violet staining for non-ampullary duodenal epithelial tumors.

OBJECTIVES: Little is known about the usefulness of magnifying endoscopy with crystal violet staining (ME-CV) for the diagnosis of duodenal tumors. We assessed the ability of ME-CV to distinguish Vienna classification (VCL) category 4/5 (C4/5) from category 3 (C3) non-ampullary duodenal epithelial tumors (NADETs). METHODS: A total of 76 NADETs were studied. We retrospectively analyzed the diagnostic values of the white light endoscopy (WLE) scoring system and the ME-CV algorithm with receiver operating characteristic (ROC) curves, and three endoscopists calculated the sensitivity, specificity, accuracy, and the area under the curve (AUC) of each. The diagnostic values were tested among NADETs overall and among subgroups of tumors with gastric, gastrointestinal or intestinal mucin phenotypes. Inter-observer agreement of the diagnostic results was also calculated. RESULTS: According to the VCL, 54 lesions (71.1%) were regarded as C3 and 22 lesions (28.9%) as C4/5. The sensitivity, specificity, accuracy and AUC of ME-CV were higher than those of the WLE scoring system (63.6 vs 54.5, 85.2 vs 75.9, 78.9 vs 69.7, 0.744 vs 0.652, respectively). Inter-observer agreements of the WLE scoring system and ME-CV were both moderate (kappa 0.45 and 0.41). ME-CV had higher sensitivity, specificity, accuracy and AUC than those of the WLE scoring system among the gastric and intestinal phenotypes of NADETs. CONCLUSIONS: ME-CV is appropriate for the diagnosis of C4/5 and C3 NADETs.

Long-term outcomes and prognostic factors with non-curative endoscopic submucosal dissection for gastric cancer in elderly patients aged ≥ 75 years.

BACKGROUND: Little is known about the long-term outcomes and prognostic factors with non-curative endoscopic submucosal dissection (ESD) in elderly patients with early gastric cancer. METHODS: Clinicopathological findings and long-term outcomes were evaluated in 87 patients with early gastric cancer (EGC) aged ≥ 75 years who were treated with non-curative ESD. Prognostic factors for overall survival (OS) were analyzed with the Kaplan-Meier method and a Cox proportional hazards model. RESULTS: During the follow-up period, among 27 patients who died of any cause, only one patient died of gastric cancer. OS probabilities after 3 and 5 years were 89.7% and 79.3%, respectively. Univariate analyses revealed that Eastern Cooperative Oncology Group performance status 2-3, Charlson comorbidity index (CCI) ≥ 3, neutrophil/lymphocyte ratio ≥ 3.3, prognostic nutritional index < 44.8, distal tumor location and macroscopically depressed or flat configuration were associated with poor OS. Cox multivariate analysis revealed high CCI (≥ 3) to be an independent prognostic factor associated with OS (hazard ratio: 2.63, 95% confidence interval [CI] 1.06-6.49, P = 0.037). CONCLUSIONS: CCI may be a useful parameter for decision-making regarding additional surgery for elderly patients with gastric cancer treated by non-curative ESD.

Immunohistochemical analysis of the epithelial to mesenchymal transition in uterine carcinosarcoma.

OBJECTIVE: Uterine carcinosarcoma (UCS) is a highly aggressive neoplasm that is composed of an intricate admixture of carcinomatous and sarcomatous elements. The relationship between UCS and the epithelial to mesenchymal transition (EMT) has been reported. In this study, we examined how expression of E-cadherin was associated with the expression of EMT-related proteins in UCS. METHODS: UCS samples were histologically divided into three components: carcinomatous, transitional, and sarcomatous regions. Next, we examined the expression of E-cadherin and EMT-related proteins, including SNAI2, ZEB1, and TWIST1, in each component of the UCS using immunohistochemistry. The expression score was determined by combining the staining intensity and staining area of the target cells. RESULTS: The expression score of E-cadherin was significantly lower in transitional and sarcomatous components than in the carcinomatous component. In addition, a significant difference in the low expression score of E-cadherin between transitional and sarcomatous components (transitional > sarcomatous components) was found. There were significant differences between the expression scores of ZEB1 in the three components (sarcomatous > transitional > carcinomatous components). However, no difference in the expression of TWIST1 between the components was found. Conversely, the expression level of SNAI2 was higher in sarcomatous or transitional components than in the carcinomatous component. However, a significant difference between the transitional and sarcomatous components was not detected. CONCLUSION: These results suggest that the EMT plays an essential role in the pathogenesis of UCS.

Clinicopathological Features and Magnifying Chromoendoscopic Findings of Non-Ampullary Duodenal Epithelial Tumors.

BACKGROUND AND AIMS: We aimed to investigate an association between clinicopathological features, including immunohistochemical mucin phenotypes, and magnifying chromoendoscopic findings with crystal violet staining (ME-CV) in non-ampullary duodenal epithelial tumors (NADETs). METHODS: A total of 55 patients with NADET were divided into 3 groups by mucin phenotype: intestinal, gastrointestinal, or gastric. ME-CV findings were classified into 4 patterns: convoluted, leaf-like, reticular/sulciolar, and pinecone. The clinicopathological features and ME-CV findings were compared among the mucin phenotypes. RESULTS: Tumors of the gastric type were located in the duodenal bulb (p < 0.001), and contained pyloric gland adenoma (p < 0.001) more frequently than the other types. White-light endoscopy indicated that milk-white mucosa was less frequent in tumors of the gastric type than in those of the gastrointestinal type (p = 0.006) and the intestinal type (p < 0.001). ME-CV findings were significantly different between the gastric type and the other type (p = 0.028). Totally, 5 of 8 tumors of the gastric type manifested a pinecone pattern, 4 of which were compatible with pyloric gland adenoma. CONCLUSIONS: The endoscopic findings of NADETs differ according to mucin phenotype. A pinecone pattern under ME-CV may be characteristic of NADETs of the gastric type, especially pyloric gland adenoma.

Case of complete response to neoadjuvant therapy using nivolumab in a patient with metastatic renal cell carcinoma.

Here, we report a case of a 68-year-old woman with cT4N0M1 (liver invasion and multiple lung metastases) metastatic renal cell carcinoma. We could carry out less invasive nephrectomy with partial hepatectomy because nivolumab administration as second-line therapy reduced the primary tumor remarkably. To the best of our knowledge, this is the first report of the use of nivolumab before carrying out surgery, and histological findings showed a pathological complete response.

Analysis of PIK3CA mutations and PI3K pathway proteins in advanced gastric cancer.

BACKGROUND: Although surgery and chemotherapy have extended advanced gastric cancer patient survival, some patients still experience relapse and metastasis. We postulated that PI3K pathway proteins could be prognostic biomarkers for the advanced gastric cancer patients. METHODS: A retrospective cohort of 160 advanced gastric cancer patients receiving potentially curative surgery with/without chemotherapy was investigated for PIK3CA mutation and PI3K pathway protein level in the context of overall survival and relapse-free survival. RESULTS: Thirteen patients (13 of 111, 11.7%) had PIK3CA mutations in codon 545, whereas one patient (1 of 94, 1.1%) had a mutation in PIK3CA codon 1047. PI3K pathway protein immunohistochemistry demonstrated that phosphorylated AKT positive [p-AKT (+)] patients in the surgery-only group had a good prognosis in terms of overall survival and relapse-free survival. No significant association between PIK3CA mutations and PI3K pathway protein level was seen. CONCLUSIONS: This study revealed that (1) PIK3CA hotspot mutations occurred with low frequency in gastric cancer; (2) PIK3CA hotspot mutations were not directly associated with PI3K pathway activation; and (3) p-AKT (+) may be a biomarker for better outcomes for gastric cancer patients undergoing gastrectomy regardless of the PIK3CA mutation status.