mTOR Signaling Combined with Cancer Stem Cell Markers as a Survival Predictor in Stage II Colorectal Cancer

Purpose@#Wnt and mammalian target of rapamycin (mTOR) are major molecular signaling pathways associated with the development and progression of tumor, as well as the maintenance and proliferation of cancer stem cells (CSCs), in colorectal cancer (CRC). Identifying patients at risk of poor prognosis is important to determining whether to add adjuvant treatment in stage II CRC and thus improve survival. In the present study, we evaluated the prognostic value of Wnt, mTOR, and CSC markers as survival predictors in stage II CRC. @*Materials and Methods@#We identified 148 cases of stage II CRC and acquired their tumor tissue. Tissue microarrays for immunohistochemical staining were constructed, and the expressions of CD166, CD44, EphB2, β-catenin, pS6 were evaluated using immunohistochemical staining. @*Results@#The expressions of CD166 (p=0.045) and pS6 (p=0.045) and co-expression of pS6/CD166 (p=0.005), pS6/CD44 (p=0.042), and pS6/CD44/CD166 (p=0.013) were negatively correlated with cancer-specific survival. Cox proportional hazard analysis showed the combination of CD166/pS6 [hazard ratio, 9.42; 95% confidence interval, 2.36–37.59; p=0.002] to be the most significant predictor related with decreased cancer-specific survival. In addition, co-expression of CD44/CD166 (p=0.017), CD166/ β-catenin (p=0.036), CD44/β-catenin (p=0.001), and CD44/CD166/β-catenin (p=0.001) were significant factors associated with liver metastasis. @*Conclusion@#Specific combinations of CSC markers and β-catenin/mTOR signaling could be a significant predictor of poor survival in stage II CRC.

Inter-observer Reproducibility in the Pathologic Diagnosis of Gastric Intraepithelial Neoplasia and Early Carcinoma in Endoscopic Submucosal Dissection Specimens: A Multi-center Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance. MATERIALS AND METHODS: We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions. RESULTS: The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important. CONCLUSION: The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.

Molecular Classification of Colorectal Cancers and Clinical Application / 대한소화기학회지

The molecular genetics of colorectal cancers (CRCs) is among the best understood of common human cancers. It is difficult to predict the prognosis and/or to predict chemoresponding in CRC patients. At present, prognosis is based predominantly on the tumor stage and pathological examination of the disease. Molecular classification of CRCs, based on genomics and transcriptomics, proposed that CRCs can be classified into at least three-to-six subtypes, depending on the gene expression pattern, and groups of marker genes representing to each subtype have also been reported. Gene expression-based subtyping is now widely accepted as a relevant source of disease stratification. We reviewed the previous studies on CRC subtyping, international consortium dedicated to large-scale data sharing and analytics recently established four consensus molecular subtypes with distinguishing features. Predictive markers identified in these studies are under investigation and large-scale clinical evaluations of molecular markers are currently in progress.

Growth Patterns of Signet Ring Cell Carcinoma of the Stomach for Endoscopic Resection

BACKGROUND/AIMS: It is difficult to precisely detect the lateral margin during endoscopic submucosal dissection (ESD) for signet ring cell carcinoma (SRC) because SRC often expands to lateral direction through the lamina propria. Thus, the aim of this study was to classify the intramucosal spreading patterns of SRC and to analyze the patients' clinicopathological findings according to the spreading patterns. METHODS: The intramucosal spreading patterns of SRC were classified as expansive or infiltrative types. A total of 100 surgical and 42 ESD specimens were reviewed. RESULTS: In the surgical specimens, the proportions of expansive and infiltrative types were 44% and 56%, respectively. The infiltrative type was more commonly associated with old age, atrophy, and intestinal metaplasia in surrounding mucosa and the absence of Helicobacter pylori compared with the expansive type. In ESD specimens, the proportions of expansive and infiltrative types were each 50%. When lateral margin-positive lesions were compared with -negative lesions, larger size, residual lesion, and the lack of a neutrophil infiltration were more significantly associated with lateral margin-positive lesions. All cases with residual tumors in lateral margin-positive lesions were classified as the infiltrative type. CONCLUSIONS: SRC surrounded with atrophy and/or intestinal metaplasia often spreads subepithelially in the margin. This finding may suggest that a larger safety margin is necessary in this type during ESD.

Usefulness of Immunohistochemistry for Microsatellite Instability Screening in Gastric Cancer

BACKGROUND/AIMS: The usefulness of immunohistochemistry to screen for the microsatellite instability (MSI) phenotype in gastric cancer remains unclear. Moreover, the prognostic value of MSI phenotypes in gastric cancer has been debated. METHODS: The clinicopathologic parameters and survival outcomes of 203 MSI-high (MSI-H) and 261 microsatellite-stable (MSS) advanced gastric cancers (AGCs) were compared. Next, we compared the immunohistochemistry results for hMLH1 and hMSH2 with those of a polymerase chain reaction (PCR)-based method. Kaplan-Meier curves and a Cox proportional hazard regression model were used to conduct survival analyses. RESULTS: The MSI-H AGCs were correlated with older age (p<0.001), female gender (p=0.018), distal location (p<0.001), larger size (p=0.016), and intestinal type (p<0.001). Multivariate analysis revealed that the MSI-H phenotype was an independent favorable factor that was related to overall survival in patients with AGC (p<0.001). Compared with the PCR-based analysis, immunohistochemistry exhibited high sensitivity (91.1%) and specificity (98.5%) in the detection of MSI phenotypes. CONCLUSIONS: MSI-H gastric cancers have distinct clinicopathologic features and better prognoses, which suggests the necessity of MSI analysis in gastric cancer. Immunohistochemistry can be a useful and reliable screening method in the assessment of MSI status in gastric cancer.

Helicobacter pylori Eradication Reduces the Metachronous Recurrence of Gastric Neoplasms by Attenuating the Precancerous Process

PURPOSE: The importance of Helicobacter pylori eradication after endoscopic resection (ER) of gastric neoplasms remains controversial. In this study, we clarified the importance of H. pylori eradication for metachronous lesions after ER. MATERIALS AND METHODS: This study included 3,882 patients with gastric neoplasms who underwent ER. We included patients infected with H. pylori who received eradication therapy. Among them, 34 patients with metachronous lesions after ER and 102 age- and sex-matched patients (nonmetachronous group) were enrolled. Background mucosal pathologies such as atrophy and intestinal metaplasia (IM) were evaluated endoscopically. The expression levels of CDX1, CDX2, Sonic hedgehog (SHH), and SOX2 were evaluated based on H. pylori eradication and the development of metachronous lesions. RESULTS: The eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.036). Open-type atrophy (P=0.003) and moderate-to-severe IM (P=0.001) occurred more frequently in the metachronous group. In patients with an initial diagnosis of dysplasia, the eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.002). In addition, open-type atrophy was more frequent in the metachronous group (P=0.047). In patients with an initial diagnosis of carcinoma, moderate-to-severe IM occurred more frequently in the metachronous group (P=0.003); however, the eradication failure rate was not significantly different between the two groups. SHH and SOX2 expression was increased, and CDX2 expression was decreased in the nonmetachronous group after eradication (P<0.05). CONCLUSIONS: Open-type atrophy, moderate-to-severe IM, and H. pylori eradication failure were significantly associated with metachronous lesions. However, eradication failure was significantly associated with dysplasia, but not carcinoma, in the metachronous group. Thus, H. pylori eradication may play an important role in preventing metachronous lesions after ER for precancerous lesions before carcinomatous transformation.

Clinical Impact of Tumor Regression Grade after Preoperative Chemoradiation for Locally Advanced Rectal Cancer: Subset Analyses in Lymph Node Negative Patients

BACKGROUND: We investigated the prognostic significance of tumor regression grade (TRG) after preoperative chemoradiation therapy (preop-CRT) for locally advanced rectal cancer especially in the patients without lymph node metastasis. METHODS: One-hundred seventy-eight patients who had cT3/4 tumors were given 5,040 cGy preoperative radiation with 5-fluorouracil/leucovorin chemotherapy. A total mesorectal excision was performed 4-6 weeks after preop-CRT. TRG was defined as follows: grade 1 as no cancer cells remaining; grade 2 as cancer cells outgrown by fibrosis; grade 3 as a minimal presence or absence of regression. The prognostic significance of TRG in comparison with histopathologic staging was analyzed. RESULTS: Seventeen patients (9.6%) showed TRG1. TRG was found to be significantly associated with cancer-specific survival (CSS; P = 0.001) and local recurrence (P = 0.039) in the univariate study, but not in the multivariate analysis. The ypN stage was the strongest prognostic factor in the multivariate analysis. Subgroup analysis revealed TRG to be an independent prognostic factor for the CSS of ypN0 patients (P = 0.031). TRG had a stronger impact on the CSS of ypN (-) patients (P = 0.002) than on that of ypN (+) patients (P = 0.521). In ypT2N0 and ypT3N0, CSS was better for TRG2 than for TRG3 (P = 0.041, P = 0.048), and in ypN (-) and TRG2 tumors, CSS was better for ypT1-2 than for ypT3-4 (P = 0.034). CONCLUSION: TRG was found to be the strongest prognostic factor in patients without lymph node metastasis (ypN0), and different survival was observed according to TRG among patients with a specific histopathologic stage. Thus, TRG may provide an accurate prediction of prognosis and may be used for f tailoring treatment for patients without lymph node metastasis.

Expression of Epstein-Barr Virus Gene and Clonality of Infiltrated T Lymphocytes in Epstein-Barr Virus-associated Gastric Carcinoma

BACKGROUND: Epstein-Barr virus associated gastric lymphoepithelioma-like carcinoma (LELC) is characterized by the intensive infiltration of lymphoid cells, the presence of EBV, and the better prognosis over typical adenocarcinoma. Thus, it was assumable that viral latent proteins may be responsible for the recruitment of a certain T cell repertoire to EBV-associated gastric carcinoma. METHODS: To examine above possibility, EBV gene expression in gastric carcinoma tissues and usage of TCR among the tumor infiltrating lymphocytes were analyzed. RESULTS: EBV specific DNA and EBERs RNA were detected in 4 out of 30 patients. RT-PCR analysis revealed that all 4 of EBV-positive tumor tissues expressed EBNA1 mRNA and BARTs and LMP2a was detected only one sample out of 4. However, the EBNA2 and LMP-1 transcripts were not detected in these tissues. CD8+ T cells were the predominant population of infiltrating lymphocytes in the EBV-positive gastric carcinoma. According to spectra type analysis of infiltrating T cells, 10 predominant bands were detected by TCR Vbeta CDR3 specific RT-PCR from 4 EBV-positive tumor tissues. Sequence analysis of these bands revealed oligoclonal expansion of T cells. CONCLUSION: These findings suggest that clonally expanded T cells in vivo might be a population of cytotoxic T cells reactive to EBV-associated gastric carcinoma.

Validation of Gene Expression Changes of Osteopontin and MMP-1 in Primary and Metastatic Colorectal Carcinomas

BACKGROUND: Metastasis is one of the most important characteristics of cancer in terms of its impact on patient survival. Unfortunately, identification of altered genes during tumor metastasis is limited. METHODS: Using high-throughput microarrays containing 19K spotted human oligonucleotides, gene expression of primary and matched metastatic colon cancer were compared in previous study. Although DNA microarray analysis did not demonstrate complete classification of primary and metastatic carcinoma, 80 differentially expressed genes were identified. Among these, expression of osteopontin, matrix metalloproteinase-1 (MMP-1) and serpin A1 was assessed using immunohistochemistry in a validation set containing 43 pairs from tissue microarrays. RESULTS: The expression of osteopontin was significantly higher in metastatic carcinoma than in primary carcinoma, as indicated by mRNA expression. The expression of MMP-1 was significantly lower in metastatic carcinoma. Expression of serpin A1 was not correlated with the microarray results. CONCLUSIONS: Osteopontin and MMP-1 expression successfully classified primary and metastatic colorectal carcinomas and further studies on their clinical application is encouraged.

Serial Episodes of Gastric and Cecal Perforation in a Patient with Behcet's Disease Involving the Whole Gastrointestinal Tract: A Case Report / 대한소화기학회지

Behcet's disease (BD) has been recognized as multi-systemic chronic vasculitic disorder of recurrent inflammation, characterized by the involvement of multiple organs and resulting in orogenital ulcers, uveitis, and skin lesions. Involvement of the central nervous system, vessels, and intestines in BD often leads to a poor prognosis. Digestive manifestations in BD have been reported in up to 1-60% of cases, although the rate varies in different countries. The most frequent extra-oral sites of gastrointestinal involvement are the ileocecal region and the colon. Gastric or esophageal involvement is reported to be very rare. Moreover, there have been no reports on the simultaneous involvement of the esophagus, stomach, ileum, and colon. Here, we present a 55-year-old Korean man with intestinal BD and multiple ileal and colonic ulcerations complicated by perforation, gastric ulcer with bleeding followed by perforation, and esophageal ulcers with bleeding.

Clinicopathologic Characteristics of Left-Sided Colon Cancers with High Microsatellite Instability

BACKGROUND: High microsatellite instability (MSI-H) colorectal carcinomas (CRCs) with numerous mutations in the microsatellite sequence are characterized by a right-sided preponderance, frequent peritumoral and intratumoral lymphocytic infiltration, and frequent mucin production. However, no study has correlated anatomic site and type of genetic changes with clinicopathologic changes. METHODS: We analyzed the histopathologic features of 135 MSI-H CRCs and compared them to 140 microsatellite stable (MSS) CRCs. Histopathologic changes in MSI-H were further analyzed according to anatomic sites and genetic changes. RESULTS: MSI-H CRCs showed previously reported clinicopathologic findings; a right-sided preponderance, an increased number of mucinous carcinomas, and peritumoral lymphoid reactions (p<0.001 for each variable). Increased serum CEA levels showed an MSS CRC preponderance (p=0.013). We further analyzed the histologic differences between right- and left-sided MSI-H tumors. We found that MSI-H CRCs on both sides had similar clinicopathologic findings, except for higher tumor stage (p=0.048) and less frequent abnormal CEA levels in left-sided MSI-H tumors (p=0.027). We found that not all clinicopathologic features were different between hereditary nonpolyposis colorectal cancers (HNPCCs) and sporadic MSI-H CRCs. CONCLUSIONS: These findings indicate that MSI-H CRCs of the left colon have similar clinicopathologic characteristics as right-sided MSI-H CRCs. We did not find any significant clinicopathological difference between HNPCCs and sporadic MSI-H CRCs.

Intestinal Endometriosis Mimicking Carcinoma of Rectum and Sigmoid Colon: A Report of Five Cases

Among women with intestinal endometriosis, the sigmoid colon and rectum are the most commonly involved areas. Sometimes, the differential diagnosis of colorectal endometriosis from carcinoma of the colon and rectum is difficult due to similar colonoscopic and radiologic findings. From October 2002 to September 2007, we performed five operations with curative intent for rectal and sigmoid colon cancer that revealed intestinal endometriosis. Colonoscopic and radiologic findings were suggestive of carcinoma of rectum and sigmoid colon, such as rectal cancer, sigmoid colon cancer and gastrointestinal stromal tumor (GIST). Anterior resection was performed in two patients, low anterior resection was performed in one patient and laparoscopic low anterior resection was done in two patients. We suggest to consider also intestinal endometriosis in reproductive women presenting with gastrointestinal symptoms and an intestinal mass of unknown origin.

Achalasia Combined with Esophageal Cancer Treated by Concurrent Chemoradiation Therapy

Achalasia is a rare neurological deficit of the esophagus that produces an impaired relaxation of the lower esophageal sphincter and decreased motility of the esophageal body. Achalasia is generally accepted to be a pre-malignant disorder, since, particularly in the mega-esophagus, chronic irritation by foods and bacterial overgrowth may contribute to the development of dysplasia and carcinoma. We present a case of a 51-year-old man with achalasia combined with esophageal cancer who has had dysphagia symptoms for more than 20 years. Since there was a clinically high possibility of supraclavicular lymph node metastasis, concurrent chemoradiation therapy was scheduled. After the third cycle of chemoradiation therapy, transthoracic esophageolymphadenectomy was performed. Histopathological examination of the main esophagus specimen revealed no residual carcinoma. And the entire regional lymph node areas were free of carcinoma except for one azygos metastatic lymph node. In summary, achalasia is a predisposing factor for esophageal squamous cell carcinoma. Although surveillance endoscopy in achalasia patients is still controversial, periodic screening for cancer development in long-standing achalasia patients might be advisable.

Needle Knife-assisted Endoscopic Polypectomy for a Large Inflammatory Fibroid Colon Polyp by Making Its Stalk into an Omega Shape Using an Endoloop

Colonic inflammatory fibroid polyp (IFP) is an uncommon benign polypoid lesion, which is composed of fibroblasts, numerous small vessels and edematous connective tissue with marked eosinophilic inflammatory cell infiltration. This condition is frequently detected in the stomach and small intestine, but uncommon in the colon. Although IFP is a benign lesion, surgical resections are performed in most colonic cases because the polyps are usually too large to resect endoscopically. Only three patients underwent endoscopic polypectomy in our literature reviews. Here, we present a case of IFP in the descending colon successful endoscopically resected using a novel technique of trapping its stalk with an endoloop, forming the stalk into an omega shape, and then dissecting the stalk with a needle knife.

Black Esophagus Associated with Alcohol Abuse

Black esophagus is a rare condition of the esophagus that manifests as endoscopic findings of black-colored esophageal mucosa, which is usually caused by acute esophageal necrosis. We report a case of alcoholic patient who developed black esophagus. The 85-year-old man was admitted to Severance Hospital due to copious hematemesis over 2 days. Upper gastrointestinal endoscopy showed black-colored mucosa in the distal esophagus. Endoscopic biopsies of the esophagus revealed necrotic tissue, without any viable cells. Follow-up upper gastrointestinal endoscopy performed after supportive care with a proton-pump inhibitor, sucralfate, and total parenteral nutrition resulted in the remarkable healing of the esophageal wall with no complications.

Progressive Suppression of Selenium Binding Protein 1 in Gastric Adenoma and Adenocarcinoma

BACKGROUND: Human selenium binding protein 1 (SELENBP1) is a protein that binds selenium as a cofactor. The decreased expression of SELENBP1 in several types of carcinomas and its association with a poor prognosis have previously been reported on. In this study, we evaluated the expression of SELENBP1 in low-grade and high-grade epithelial dysplasia/ adenomas and adenocarcinomas. METHODS: We analyzed 45 cases of low-grade epithelial dysplasia/adenomas, 42 cases of high-grade epithelial dysplasia/adenomas and 64 cases of adenocarcinomas and all of them were obtained from endoscopic mucosal resection or endoscopic submucosal dissection. We analyzed all of them for their SELENBP1 expression by immunohistochemistry. Eight triple-paired cases of gastric mucosa, adenoma and adenocarcinoma from the same patient were selected for RT-PCR analysis. RESULTS: There was a progressive decrease in the expression of SELENBP1 from the low-grade dysplasia/adenomas (42/45, 93%) to the high-grade dysplasia/adenomas (29/42, 69%) and finally to the adenocarcinomas (24/64, 37%), (p<0.001). The progressive decrease in the SELENBP1 expression was also evident in the eight paired cases that were analyzed by RT-PCR. CONCLUSIONS: Our findings demonstrate that the SELENBP1 expression is suppressed in gastric epithelial dysplasia/adenomas and adenocarcinomas. The suppression of SELENBP1 was significantly more frequent and severer in the adenocarcinomas than that in the low-grade dysplasia/ adenomas, and this implies that the suppression of SELENBP1 is a late event in gastric carcinogenesis.

Clinical Significance of E-cadherin and beta-catenin Complex Expression in T2 Colorectal Cancer

PURPOSE: Expression of adhesion molecules is significantly correlated with the invasion and the metastasis of colorectal cancer. The aim of this study is to identify the importance of the expressions of E-cadherin and beta-catenin as a prognostic factor in T2 colorectal cancer. METHODS: Forty-five cases of primary T2 colorectal cancers were selected between February 1997 and February 2000. We evaluated the membranous expressions of E-cadherin and beta-catenin by using immunohistochemisty and analyzed the relationship with various clinicopathologic parameters. RESULTS: Loss of membranous E-cadherin was significantly associated with histologic differentiation (P=0.023), vascular invasion (P<0.001), lymphatic invasion (P<0.001), and lymph-node metastases (P=0.001). Similar patterns were observed in the expression of beta-catenin. The correlation between the E-cadherin and the beta-catenin expressions was statistically significant (P<0.001). In the multivariate analysis, neither the loss of expression of E-cadherin nor beta-catenin is a risk factor affecting lymph-node metastasis in T2 colorectal cancers. However, there were significant differences in the 5-year disease-free survival rates between the positive (+/-, +) and the negative (-) expression groups of E-cadherin and beta-catenin (P=0.015, 0.03). CONCLUSIONS: This study suggests that loss of membranous expression of E-cadherin and beta-catenin molecules correlates with poor prognostic factors and indicates invasion and metastasis in T2 colorectal cancer, which, therefore, might be predictive of short survival in these patients.

A Case of More Abundant and Dysplastic Adenomas in the Interposed Colon than in the Native Colon

We report a 60-year-old woman with intramucosal adenocarcinoma arising in the interposed colon, 40 years after the esophageal reconstruction for lye induced esophageal stricture. Although synchronous adenomas were also found in the native colon where the graft was taken, the number of adenomas was greater in the interposed colon and more dysplastic, even progressed to adenocarcinoma, than that of the native colon. The microsatellite instability-testing performed in the intramucosal carcinoma from interposed colon showed absence of microsatellite instability. Changing of location and functional deman]d of colonic segment, and the exposure to different intraluminal contents might have facilitated the adenoma- carcinoma transformation in the interposed colon.

Salivary Duct Carcinoma with Mucin Containing Cells: Report of a Case Misdiagnosed as Mucoepidermoid Carcinoma on Fine Needle Aspiration Cytology / 대한세포병리학회지

Salivary duct carcinoma (SDC) is a rare primary salivary gland malignancy characterized by histological features similar to those of ductal carcinomas of the breast. It is regarded as a high-grade malignancy associated with frequent local recurrences and early distant metastases that require aggressive treatment. The typical fine needle aspiration cytology (FNAC) findings in SDC include cellular smears showing tumor cells with eccentric pleomorphic nuclei and a granular cytoplasm arranged in flat sheets or cribriform patterns against a necrotic background. However, the presence of mucin-containing cells in SDC has been rarely described. We report the FNAC findings in a patient with histologically confirmed SDC that demonstrated numerous mucin-containing cells and was subsequently misdiagnosed as a high-grade mucoepidermoid carcinoma. Here we discuss the problems involved in distinguishing SDC from high-grade mucoepidermoid carcinoma on the basis of cytologic findings alone.

Identification of Target Genes in the Endometrial Carcinomas with Microsatellite Mutator Phenotype / 대한산부인과학회지

OBJECTIVE: Recent molecular genetic studies have revealed that two major types of genomic instabilities, chromosomal instability and microsatellite instability (MSI), exist in the endometrial carcinomas. Tumors with microsatellite mutator phenotype (MMP) are caused by defects in DNA mismatch repair genes. MMP tumors are believed to progress by accumulating frameshift mutations in coding microsatellite sequences of various cancer related genes including tumor suppressor genes, apoptosis related genes and DNA repair genes. Thus, the identification of the specific target genes in the MMP endometrial carcinomas is important for the elucidation of molecular pathogenesis of endometrial carcinomas. METHODS: We classified the MMP endometrial carcinomas and evaluated the frameshift mutations of the 11 genes containing coding microsatellite sequences by using 34 endometrial carcinomas and 4 MMP endometrial carcinoma cell lines. RESULTS: MSI was found in 6 of 34 endometrial carcinomas. In the endometrial carcinoma tissues, frequent mutations were found in TAF1B (68%), HT001 (50%), SLC23A1 (50%) and ACVR II (50%) in the MMP endometrial carcinoma tissues. The other 7 genes were infrequently mutated. Mutations of these target genes were more frequent in MMP endometrial carcinoma cell lines. CONCLUSION: we identified specific target genes in MMP endometrial carcinomas. These data demonstrate the mechanism of tumor progression in the MMP endometrial carcinomas.