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1.
Article in Chinese | WPRIM | ID: wpr-936064

ABSTRACT

Immunotherapy has become an important treatment option for microsatellite instability-high (MSI-H) and mismatch repair deficient (dMMR) colorectal cancer. From late-line to first-line treatment, and even in neoadjuvant setting for early stage colorectal cancer, promising efficacy was observed with immunotherapy. In microsatellite stability (MSS) or mismatch repair proficient (pMMR) colorectal cancer, the researches of neoadjuvant immunotherapy have been conducted constantly. This paper focuses on the recent researches and progress of neoadjuvant immunotherapy for MSS or pMMR colorectal cancer. Neoadjuvant immunotherapy alone led to a good pathological response in a subset of patients. Studies of induction or consolidation immunotherapy before or after neoadjuvant chemoradiotherapy or concurrent immunotherapy during radiotherapy showed higher pathological complete remission (pCR) rates as compared to standard chemoradiotherapy. Studies on sequential dual immunotherapy after radiochemotherapy and targeted therapy combined with neoadjuvant immunotherapy are ongoing. At present, most of these are pilot studies with small sample size. More researches and long-term follow-up are needed to prove the efficacy of neoadjuvant immunotherapy in MSS or pMMR colorectal cancer.


Subject(s)
Colorectal Neoplasms/therapy , DNA Mismatch Repair/genetics , Humans , Immunotherapy , Microsatellite Repeats , Neoadjuvant Therapy
2.
Chinese Journal of Pathology ; (12): 103-107, 2022.
Article in Chinese | WPRIM | ID: wpr-935484

ABSTRACT

Objective: To investigate the relationship between the expression of four mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) and NTRK genetic fusions in colorectal cancer. Methods: The paraffin-embedded tissue blocks of 830 cases of colorectal cancer were collected at the Affiliated Drum Tower Hospital, Nanjing University Medical School, China, from 2015 to 2019. Immunohistochemical and fluorescence in situ hybridization(FISH) method were used respectively to detect the expression of mismatch repair proteins and the break-apart of NTRKs; and the relationship between the expression of mismatch repair proteins and the NTRK genetic fusions was analyzed. Results: The overall mismatch repair protein deficiency (dMMR) rate was 9.88% (82/830), the mismatch repair proteins proficiency (pMMR) rate was 90.12%(748/830). The total deficiency rate of MLH1 protein was 9.04% (75/830), hPMS2 protein deficiency rate was 9.04% (75/830), MSH2 protein deficiency rate was 2.53% (21/830), MSH6 protein deficiency rate was 4.10% (34/830), the deficiency rate of synchronous MLH1 and PMS2 were 8.67% (72/830) and the deficiency rate of synchronous MSH2 and MSH6 were 2.17% (18/830). The dMMR group was associated with tumor location, different histological subgroups, tumor differentiation, AJCC stage and N stage (P<0.05). There were six cases (7.32%) carrying NTRK fusion by FISH among the 82 cases of dMMR, but only seven cases (0.94%) carrying NTRK fusion among the 748 cases of PMMR. The NTRKs translocation by FISH in all 13 cases were further confirmed by next generation sequencing. Among the clinicopathological characteristics, only differentiation showed significant difference between NTRK fusion positive and negative groups (P<0.05). More importantly, NTRK fusion was enriched in dMMR group (7.32% vs. 0.94%). Conclusion: In dMMR colorectal cancer group, the prevalence of NTRK fusion is higher than that in pMMR group.


Subject(s)
Colonic Neoplasms , Colorectal Neoplasms/genetics , DNA Mismatch Repair/genetics , Humans , In Situ Hybridization, Fluorescence , Mismatch Repair Endonuclease PMS2/metabolism , MutL Protein Homolog 1/metabolism , MutS Homolog 2 Protein/metabolism
3.
Rev. Assoc. Med. Bras. (1992) ; 67(1): 64-70, Jan. 2021. tab, graf
Article in English | LILACS | ID: biblio-1287776

ABSTRACT

SUMMARY OBJECTIVE: Bladder cancer under the age of 40 is extremely rare. Bladder cancer development involves complex and multi-stage processes, one of which is the DNA damage repair mechanism. In this retrospective study, we aimed to evaluate the histopathological features of bladder urothelial carcinoma seen in patients under 40 years of age and tumor microsatellite instability status using immunohistochemistry. METHODS: A total of 50 patients under the age of 40 with urothelial bladder carcinoma from two different centers in the same country were included. Expression of the mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 was analyzed by immunohistochemistry. RESULTS: Age at the time of diagnosis ranged from 17 to 40 years old. Most tumors were non-invasive papillary urothelial carcinoma. Two cases had nuclear loss of MSH-6 and PMS-2. We observed that tumor grade, tumor stage, presence of tumor differentiation, and infiltrative growth pattern of the tumor have significant impact on prognosis, but microsatellite instability does not have an effective role in bladder carcinogenesis in young patients. CONCLUSIONS: Our results indicate that the presence of microsatellite instability is not related to the low tumor grade and stage in urothelial neoplasms in young patients, suggesting that urothelial carcinoma of the bladder in young patients may represent a genetically stable form of neoplasia.


Subject(s)
Humans , Adolescent , Adult , Young Adult , Carcinoma, Transitional Cell/genetics , Microsatellite Instability , Urinary Bladder/metabolism , Retrospective Studies , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , DNA Mismatch Repair
4.
Article in Chinese | WPRIM | ID: wpr-942907

ABSTRACT

Objective: To analyze the expression of mismatch repair (MMR) protein and the EB virus infection in gastric adenocarcinoma, and to examine the association of MMR expression and EB virus infection with clinicopathological parameters. Methods: A case-control study was performed. Clinicopathological data of patients who was pathologically diagnosed as gastric adenocarcinoma, received radical gastrectomy and had complete clinicopathological data from August 2017 to April 2020 in Tianjin Medical University Cancer Institute and Hospital were retrospectively collected and analyzed. The immunohistochemistry (IHC) of MMR proteins and in situ hybridization (ISH) of Epstein-Barr virus encoded RNA (EBER) were reviewed. The associations of MMR and EBER results with clinicopathological parameters were analyzed. The main observations of the study were MMR and EBER expression, and association of MMR and EBER results with clinicopathological parameters. Results: Eight hundred and eighty-six patients were enrolled, including 98 patients who received preoperative neoadjuvant chemoradiotherapy. Of 886 patients, 613 (69.2%) were males and the median age was 60 (22-83) years; 831 (93.8%) were mismatch repair proficiency (pMMR), and 55 (6.2%) were mismatch repair deficiency (dMMR). In dMMR group, 47 cases (85.5%) had the deficiency of both MLH1 and PMS2, 1 case (1.8%) had the deficiency of both MSH2 and MSH6, 4 cases (7.3%) had the deficiency only in PMS2, 2 cases (3.6%) had the deficiency only in MSH6, and 1 case (1.8%) had the deficiency only in MSH2. The deficiency rates of PMS2, MLH1, MSH6 and MSH2 were 5.8% (51/886), 5.3% (47/886), 0.3% (3/886) and 0.2% (2/886), respectively. Among the 871 cases with EBER results, 4.9% (43/871) were positive EBER. Univariate analysis showed that dMMR was more frequently detected in female patients (χ(2)=10.962, P=0.001), cancer locating in the antrum (χ(2)=9.336,P=0.020), Lauren intestinal type (χ(2)=9.718, P=0.018), stage T3 (χ(2)=25.866, P<0.001) and TNM stage II (χ(2)=15.470, P=0.002). The ratio of dMMR was not significantly associated with age, tumor differentiation, histological type, lymph node metastasis, distant metastasis or Her-2 immunohistochemical score (all P>0.05). Compared with negative EBER, positive EBER was more frequent in male patients (χ(2)=9.701, P=0.002), cancer locating in gastric fundus and corpus (χ(2)=17.964, P<0.001), gastric cancer with lymphoid stroma (χ(2)=744.073, P<0.001) and poorly differentiated cancer (χ(2)=13.739, P=0.010). Positive EBER was not significantly associated with age, depth of invasion, lymph node metastasis, distant metastasis, TNM stage or Her-2 immunohistochemical score (all P>0.05). In addition, all dMMR cases were EBER negative, and all cases of positive EBER were pMMR. Conclusions: The positive EB virus status is mutually exclusive with dMMR, indicating that different molecular subtypes of gastric adenocarcinoma are involved in different molecular pathways in tumorigenesis and progression. The overlapping of dMMR or positive EBER status and positive Her-2 expression is found in some cases of gastric adenocarcinoma. Patients with gastric adenocarcinoma after radical surgery should be tested for MMR status if they are female, the tumor locates in gastric antrum, the TNM staging is stage II or T3, or if the Lauren classification is intestinal type. And if patients are male, the tumor locates in the gastric fundus and corpus, the cancer is lymphoid stroma, or poor differentiated, the expression of EBER should be detected. Results of our study may provide evidence for further decision-making of clinical treatment.


Subject(s)
Adenocarcinoma , Case-Control Studies , DNA Mismatch Repair , Epstein-Barr Virus Infections , Female , Herpesvirus 4, Human , Humans , Male , Middle Aged , Mismatch Repair Endonuclease PMS2/metabolism , MutL Protein Homolog 1/genetics , MutS Homolog 2 Protein/metabolism , Retrospective Studies , Stomach Neoplasms
5.
Article in Chinese | WPRIM | ID: wpr-880786

ABSTRACT

OBJECTIVE@#To explore the clinicopathological features and types of genic mutations in DNA mismatch repair (MMR) in colorectal cancer (CRC).@*METHODS@#Immunohistochemistry was used to determine the expression of MMR proteins in 1394 patients with CRC, and PCR-capillary electrophoresis (PCR-CE) was used to detect microsatellite instability (MSI) in 106 cases of defective MMR (dMMR), 46 cases of proficient MMR (pMMR) with heterogeneous expression and 147 randomly selected cases of pMMR. The relationship between the expressions of MMR proteins and the clinicopathological features of the patients was evaluated. The consistency between the results of immunohistochemistry and PCR-CE was assessed.@*RESULTS@#Immunohistochemical staining showed an incidence of dMMR of 7.6% in the patients. The main type of dMMR was co-deletion of MLH1 and PMS2, accounting for 55.7% of the total dMMR cases. The deletion of MMR proteins was significantly correlated with the patients' age, tumor location, tumor size, gross type, histological type, degree of differentiation, lymph node status and TNM stage (@*CONCLUSIONS@#The main type of dMMR is co-deletion of MLH1 and PMS2 in patients with colorectal cancer. dMMR colorectal cancer has typical clinicopathological features and a lower incidence in China than in Western countries. The results of immunohistochemistry and PCR-CE are highly consistent for detecting dMMR in colorectal cancer patients.


Subject(s)
China , Colorectal Neoplasms/genetics , DNA Mismatch Repair/genetics , Humans , Microsatellite Instability
6.
J. coloproctol. (Rio J., Impr.) ; 39(3): 223-230, June-Sept. 2019. tab
Article in English | LILACS | ID: biblio-1040328

ABSTRACT

ABSTRACT Background: Colorectal cancer survival is better in hereditary nonpolyposis colorectal cancer patients than in sporadic colorectal cancer patients and even for hereditary nonpolyposis colorectal cancer with colorectal cancer is not consensual that extensive colectomy is preferable to partial colectomy. This study analyzes and compares the long-term results of these two groups of patients submitted to curative subtotal colectomy or total colectomy. Methods: Between 2002 and 2018, 68 patients with colorectal cancer without familial adenomatous polyposis were submitted to a total or subtotal colectomy in a single tertiary center. The patients were divided in two groups: hereditary nonpolyposis colorectal cancer patients (with Amsterdam criteria) and sporadic colorectal cancer patients (the others). The presence of Amsterdam criteria for hereditary nonpolyposis colorectal cancer and germline mutation for mismatch repair genes was confirmed by clinical records. Results and survival were analyzed following surgery. Results: We obtained a sporadic colorectal cancer group with 31 patients and a hereditary nonpolyposis colorectal cancer group with 37 patients. The two groups differ in age but not in gender, tumor stage or surgical morbidity. The overall survival and disease-free survival were good in both groups but even better for hereditary nonpolyposis colorectal cancer group with statistical significance when comparing the two groups. Conclusion: Total or subtotal colectomy for colorectal cancer provides a good survival. These surgical procedures should be considered the first option for colorectal cancer in young hereditary non polyposis colorectal cancer patients. In those cases, they provide good long-term results, avoiding the risk of metachronous colorectal cancer and the surveillance is restricted only to the remaining need for rectum.


RESUMO Introdução: A sobrevivência do cancro colorretal é melhor em pacientes com cancro colorretal hereditário não associado a polipose do que em pacientes com cancro colorretal esporádico. Mesmo em casos de cancro colorretal hereditário sem polipose, a preferência pela colectomia total em relação à parcial não é consensual na literatura. Este estudo analisa e compara os resultados a longo prazo destes dois grupos de pacientes submetidos à colectomia curativa subtotal ou total. Métodos: Entre 2002 e 2018, 68 pacientes com cancro colorretal sem polipose adenomatosa familiar foram submetidos a colectomia total ou subtotal em um único centro terciário. Os pacientes foram divididos em dois grupos: aqueles com cancro colorretal hereditário sem polipose (de acordo com os critérios de Amsterdão) e os com cancro colorretal esporádico (os demais). Os critérios de Amsterdão para cancro colorretal hereditário sem polipose e a presença de mutação germinativa para os genes de reparação de ADN foram confirmados por consulta dos registros clínicos. Os resultados e a sobrevivência foram analisados após a cirurgia. Resultados: No presente estudo, 31 pacientes foram incluídos no grupo de cancro colorretal esporádico e 37 no grupo de cancro colorretal hereditário sem polipose. Diferenças significativas foram observadas em relação à idade, mas não ao gênero, estadio do tumor ou morbilidade cirúrgica. A sobrevivência global e a sobrevivência livre de doença foram boas em ambos os grupos, mas os resultados foram ainda melhores no grupo de cancro colorretal hereditário sem polipose, com significado estatístico. Conclusão: A colectomia total ou a colectomia subtotal para o cancro colorretal proporcionam uma boa sobrevivência e devem ser consideradas a primeira opção de tratamento em pacientes jovens com cancro colorretal hereditário sem polipose. Nestes pacientes, uma cirurgia cólica mais extensa permite a obtenção de bons resultados a longo prazo; reduz o risco de cancro colorretal metácrono e restringe a vigilância endoscópica ao reto remanescente.


Subject(s)
Humans , Male , Female , Colorectal Neoplasms/surgery , Colorectal Neoplasms, Hereditary Nonpolyposis , Colectomy , Colon/pathology , DNA Mismatch Repair
7.
Cancer Research and Treatment ; : 1198-1206, 2019.
Article in English | WPRIM | ID: wpr-763160

ABSTRACT

PURPOSE: Mismatch repair (MMR) deficiency plays a critical role in rectal cancer. This study aimed to explore the associations between genetic variations in seven MMR genes and adverse events (AEs) and survival of patients with rectal cancer treated with postoperative chemoradiotherapy (CRT). MATERIALS AND METHODS: Fifty single nucleotide polymorphisms in seven MMR (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2) genes were genotyped by Sequenom MassARRAY method in 365 patients with locally advanced rectal cancer receiving postoperative CRT. The associations between genotypes and AEs were measured by odds ratios and 95% confidence intervals (CIs) by unconditional logistic regression model. The associations between genetic variations and survival were computed by the hazard ratios and 95% CIs by Cox proportional regression model. RESULTS: The most common grade ≥ 2 AEs in those 365 patients, in decreasing order, were diarrhea (44.1%), leukopenia (29.6%), and dermatitis (18.9%). Except 38 cases missing, 61 patients (18.7%) died during the follow-up period. We found MSH3 rs12513549, rs33013 and rs6151627 significantly associated with the risk of grade ≥ 2 diarrhea. PMS1 rs1233255 had an impact on the occurrence of grade ≥2 dermatitis. Meanwhile, PMS1 rs4920657, rs5743030, and rs5743100 were associated with overall survival (OS) time of rectal cancer. CONCLUSION: These results suggest that MSH3 and PMS1 polymorphisms may play important roles in AEs prediction and prognosis of rectal cancer patients receiving postoperative CRT, which can be potential genetic biomarkers for rectal cancer personalized treatment.


Subject(s)
Biomarkers , Chemoradiotherapy , Dermatitis , Diarrhea , DNA Mismatch Repair , Follow-Up Studies , Genetic Variation , Genotype , Humans , Leukopenia , Logistic Models , Methods , Odds Ratio , Polymorphism, Single Nucleotide , Prognosis , Rectal Neoplasms
8.
Chinese Journal of Oncology ; (12): 734-741, 2019.
Article in Chinese | WPRIM | ID: wpr-773350

ABSTRACT

Microsatellite instability (MSI) which resulted from the deficiency of DNA mismatch repair (MMR), is an important clinical significance in the related solid tumors, such as colorectal cancer and endometrial cancer. There are several methods to detect MSI status, including immunohistochemistry for MMR protein, multiplex fluorescent polymerase chain reaction (PCR) for microsatellite site and MSI algorithm based on next generation sequencing (NGS). The consensus elaborates the definition and clinical significance of MSI as well as the advantages and disadvantages of the three detection methods. Through this expert consensus, we hope to promote the screening which based on MSI status in malignant tumors and improve the acknowledge of clinicians about various testing methods. Thereby, they could interpret the results more accurately and provide better clinical services to patients.


Subject(s)
Antineoplastic Agents , Therapeutic Uses , China , Colorectal Neoplasms , Genetics , Pathology , Consensus , DNA Mismatch Repair , DNA Sequence, Unstable , Delivery of Health Care , Reference Standards , Endometrial Neoplasms , Female , Humans , Immunohistochemistry , Microsatellite Instability , Microsatellite Repeats , Microscopy, Fluorescence , Polymerase Chain Reaction , Practice Guidelines as Topic
9.
Article in English | WPRIM | ID: wpr-719308

ABSTRACT

OBJECTIVE: Gynecologists occasionally encounter synchronous endometrial and ovarian endometrioid carcinoma (SEO-EC) patients who show favorable prognosis than locally advanced or metastatic disease patients. This study aimed to elucidate prognostic factors of SEO-EC and identify patients who have a sufficiently low risk of recurrence without receiving adjuvant chemotherapy. METHODS: We retrospectively reviewed 46 patients with pathologically confirmed SEO-EC who underwent surgery at the National Cancer Center Hospital between 1997 and 2016. Immunohistochemical evaluation of DNA mismatch repair (MMR) protein expression were performed for both endometrial and ovarian tumors. Patient outcomes were analyzed according to clinicopathologic factors. RESULTS: From the multivariate analysis, cervical stromal invasion indicated a worse prognosis for progression-free survival (hazard ratio [HR]=6.85; 95% confidence interval [CI]=1.50–31.1) and overall survival (HR=6.95; 95% CI=1.15–41.8). Lymph node metastasis and peritoneal dissemination did not significantly affect survival. MMR deficiency was observed in 13 patients (28.3%), with both endometrial and ovarian tumors showing the same MMR expression status. MMR deficiency was not significantly associated with survival. Of 23 patients with lesions confined to only the uterine body and adnexa, only 2 had recurrence in the group receiving adjuvant therapy, while none of the 10 patients who did not receive adjuvant therapy had recurrence. CONCLUSION: SEO-EC patients with tumors localized to the uterine body and adnexa lesions had a low risk for recurrence and may not require adjuvant therapy. SEO-EC may have prognostic factors different from those of endometrial and ovarian cancer.


Subject(s)
Carcinoma, Endometrioid , Chemotherapy, Adjuvant , Disease-Free Survival , DNA Mismatch Repair , Humans , Immunohistochemistry , Lymph Nodes , Multivariate Analysis , Neoplasm Metastasis , Neoplasms, Multiple Primary , Ovarian Neoplasms , Prognosis , Recurrence , Retrospective Studies
10.
Rev. gastroenterol. Perú ; 38(3): 265-279, jul.-set. 2018. ilus, tab
Article in Spanish | LILACS | ID: biblio-1014094

ABSTRACT

Esta revisión tiene como objetivo dar a conocer los aspectos genéticos, clínicos y diagnósticos del síndrome de Lynch, además de brindar la información más relevante acerca de la asesoría genética en estos pacientes y las recomendaciones actuales para su seguimiento.


This review aims to present the genetic, clinical and diagnostic aspects of Lynch syndrome, as well as providing the most relevant information about genetic counseling in these patients and the current recommendations for their surveillance.


Subject(s)
History, 19th Century , History, 20th Century , Humans , Colorectal Neoplasms, Hereditary Nonpolyposis , Algorithms , Neoplastic Syndromes, Hereditary/diagnosis , DNA, Neoplasm/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/history , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , Biomarkers, Tumor , Risk , Endoscopy, Gastrointestinal , Risk Assessment , Genetic Heterogeneity , Penetrance , Diagnosis, Differential , Genes, Neoplasm , Microsatellite Instability , DNA Mismatch Repair/genetics , Genetic Association Studies , Genetic Counseling , Models, Genetic
11.
Article in Chinese | WPRIM | ID: wpr-771477

ABSTRACT

OBJECTIVE@#To investigate the expressions of secreted frizzled-related protein 4 (SFRP4) in stage Ⅱ DNA mismatch repair-deficient (dMMR) and mismatch repair- proficient (pMMR) colorectal cancers and explore their clinical significance.@*METHODS@#We collected fresh stage Ⅱ colon cancer tissues with different MMR status detected by immunohistochemistry (IHC). The differentially expressed mRNAs between dMMR and pMMR tumors were identified by Affymetrix Human oeLncRNA gene chip, and the expression of SFRP4 in these cancer tissues and in colorectal cancer cell lines were detected using Western blotting and real- time quantitative PCR. The apoptosis rates of HCT116 cells with and without siRNA- mediated transient SFRP4 knockdown were determined using flow cytometry. We further investigated the expression pattern of Ki-67 and its correlation with SFRP4 expression.@*RESULTS@#Compared with pMMR colon cancer tissues or cells, both dMMR colon cancer tissues (=0.014) and cells (=0.0079) showed significantly increased expression of SFRP4, which was in negative correlation with Ki-67 (=0.041). In HCT116 cells, transient SFRP4 knockdown resulted in decreased cell apoptosis, including both early apoptosis (=0.003) and late apoptosis (=0.024).@*CONCLUSIONS@#Up-regulation of SFRP4 in dMMR stage Ⅱ colon cancer promotes apoptosis and inhibits proliferation of the cancer cells, and may improve the prognosis of dMMR colon cancer.


Subject(s)
Apoptosis , Cell Proliferation , Colon , Metabolism , Pathology , Colonic Neoplasms , Genetics , Metabolism , Pathology , Colorectal Neoplasms , Genetics , Metabolism , Pathology , DNA Mismatch Repair , Gene Knockdown Techniques , HCT116 Cells , Humans , Ki-67 Antigen , Metabolism , Prognosis , Proto-Oncogene Proteins , Genetics , Metabolism , Up-Regulation
12.
Article in English | WPRIM | ID: wpr-741151

ABSTRACT

BACKGROUND: Smad4 and PTEN are prognostic indicators for various tumor types. Smad4 regulates tumor suppression, whereas PTEN inhibits cell proliferation. We analyzed and compared the performance of Smad4 and PTEN for predicting the prognosis of patients with colorectal adenocarcinoma. METHODS: Combined expression patterns based on Smad4+/– and PTEN+/– status were evaluated by immunostaining using a tissue microarray of colorectal adenocarcinoma. The relationships between the protein expression and clinicopathological variables were analyzed. RESULTS: Smad4–/PTEN– status was most frequently observed in metastatic adenocarcinoma, followed by primary adenocarcinoma and tubular adenoma (p<.001). When Smad4–/PTEN– and Smad4+/PTEN+ groups were compared, Smad4–/PTEN– status was associated with high N stage (p=.018) and defective mismatch repair proteins (p=.006). Significant differences in diseasefree survival and overall survival were observed among the three groups (Smad4+/PTEN+, Smad4–/PTEN+ or Smad4+/PTEN–, and Smad4–/PTEN–) (all p<.05). CONCLUSIONS: Concurrent loss of Smad4 and PTEN may lead to more aggressive disease and poor prognosis in patients with colorectal adenocarcinoma compared to the loss of Smad4 or PTEN alone.


Subject(s)
Adenocarcinoma , Adenoma , Cell Proliferation , Colonic Neoplasms , DNA Mismatch Repair , Humans , Prognosis
13.
Article in English | WPRIM | ID: wpr-741476

ABSTRACT

PURPOSE: There are numerous prostate cancer-related genes that involve in carcinogenesis and tumor progression. Among the genes, DNA mismatch repair genes recognize and repair misincorporated nucleotides during DNA replication. In this analysis, we evaluated the association of hMSH2 which is one of the mismatch repair genes, with risk of aggressive prostate cancer and prostate cancer recurrence. MATERIALS AND METHODS: Immunohistochemistry was performed in 46 patients who diagnosed prostate cancer and underwent radical prostatectomy between January 2006 and December 2012 at Kyung Hee University Hospital at Gangdong. We evaluated an association between the degree of hMSH2 immunohistochemical staining and various clinical variables including prostate-specific antigen (PSA), Gleason score, pathological stage, and biochemical recurrence. The intensity of immunostaining for hMSH2 was divided into 2 groups: low expression group (immunostaining score < 2) and high expression group (immunostaining score ≥2). RESULTS: Although seminal vesicle invasion was marginally associated with the degree of hMSH2 immunohistochemical staining, PSA, Gleason score, lymph node metastasis, presence of lymphatic, perineural, vascular invasion, and extracapsular extension were not associated with the degree of hMSH2 immunohistochemical staining. Furthermore, the association of biochemical recurrence free survival with hMSH2 expression was not statistically significant. CONCLUSIONS: The hMSH2 expression was marginally associated with risk of aggressive prostate cancer such as seminal vesicle invasion. Further evaluation with a larger number of cases is needed to verify these results.


Subject(s)
Base Pair Mismatch , Carcinogenesis , DNA Mismatch Repair , DNA Repair , DNA Replication , Gene Expression , Humans , Immunohistochemistry , Lymph Nodes , Neoplasm Grading , Neoplasm Metastasis , Nucleotides , Prostate , Prostate-Specific Antigen , Prostatectomy , Prostatic Neoplasms , Recurrence , Seminal Vesicles
14.
Article in English | WPRIM | ID: wpr-714693

ABSTRACT

OBJECTIVE: The risk of developing endometrial cancer (EC) and/or survival following a diagnosis of EC might differ by tumor DNA mismatch repair (MMR) status. We assessed the association between tumor MMR status (classified as MMR-proficient, somatic MMR-deficient, germline MMR-deficient) and the risk of developing EC and survival following a diagnosis of EC. METHODS: We analyzed data from women who participated in the Australian National Endometrial Cancer Study (ANECS) conducted between 2005 and 2007. Risk analyses (698 cases/691 population controls) utilized sociodemographic and lifestyle information obtained from telephone interviews at recruitment. For survival analyses (728 cases), patients' clinical data was abstracted from medical records, and survival data were obtained via linkage with the Australian National Death Index. We used logistic regression analysis to evaluate the associations between tumor MMR status and EC risk, and proportional hazards models to perform survival analyses with adjustment of known prognostic factors. RESULTS: Established risk factors for EC did not differ significantly by tumor MMR status. In analyses including all EC subtypes, overall and EC-specific survival did not differ by tumor MMR status. Among women with the most common endometrioid subtype, EC-specific survival was worse for women with somatic MMR-deficient EC compared to women with MMR-proficient EC (hazard ratio [HR]=2.18; 95% confidence interval [CI]=1.19–4.01). CONCLUSION: The risk of EC is not associated with MMR status. Accurate separation of germline from somatic causes of MMR deficiency suggests that patients with endometrioid subtype somatic MMR-deficient tumors have poorer EC-specific survival than those with MMR-proficient tumors, after accounting for other prognostic factors.


Subject(s)
Diagnosis , DNA Mismatch Repair , Endometrial Neoplasms , Female , Humans , Interviews as Topic , Life Style , Logistic Models , Medical Records , Proportional Hazards Models , Risk Factors
15.
Article in English | WPRIM | ID: wpr-714687

ABSTRACT

OBJECTIVE: Lynch syndrome is a cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes. Lynch syndrome only causes about 0.4% of cases of ovarian cancer, which suggests that universal screening may not be cost-efficient. However, the frequency of Lynch syndrome in ovarian cancer is unclear in the Asian population. The goal of the study was to investigate a screening strategy using family history. METHODS: The subjects were 129 patients with ovarian cancer. Clinical and family history were collected using a self-administered questionnaire, and Society of Gynecologic Oncology (SGO) criteria 2007 and PREMM5 were used for risk assessment. Microsatellite instability, immunohistochemistry, and methylation of MMR genes were analyzed. RESULTS: Of the 129 cases, 25 (19.4%) met the SGO criteria, and 4 of these 25 had MSI-high and MMR deficiency. Two cases had loss of MSH2 and MSH6, indicating MSH2 mutation, and the other two had loss of MLH1 and PMS2, including one without MLH1 methylation indicating MLH1 mutation. These results show that screening using family history can detect Lynch syndrome in 12.0% (3/25) of ovarian cancer cases. The 3 cases were positive for PREMM5, but negative for Amsterdam II criteria and revised Bethesda guidelines. Genetic testing in one case with MSH2 and MSH6 deficiency confirmed the diagnosis of Lynch syndrome with MSH2 mutation. CONCLUSION: This is the first study of screening for Lynch syndrome in ovarian cancer using clinical and family history in an Asian population. This approach may be effective for diagnosis in these patients.


Subject(s)
Asians , Colorectal Neoplasms, Hereditary Nonpolyposis , Diagnosis , DNA Mismatch Repair , Genetic Testing , Germ-Line Mutation , Humans , Immunohistochemistry , Mass Screening , Medical History Taking , Methylation , Microsatellite Instability , Ovarian Neoplasms , Risk Assessment
16.
Intestinal Research ; : 358-365, 2018.
Article in English | WPRIM | ID: wpr-715885

ABSTRACT

In the past two decades, besides conventional adenoma pathway, a subset of colonic lesions, including hyperplastic polyps, sessile serrated adenoma/polyps, and traditional serrated adenomas have been suggested as precancerous lesions via the alternative serrated neoplasia pathway. Major molecular alterations of sessile serrated neoplasia include BRAF mutation, high CpG island methylator phenotype, and escape of cellular senescence and progression via methylation of tumor suppressor genes or mismatch repair genes. With increasing information of the morphologic and molecular features of serrated lesions, one major challenge is how to reflect this knowledge in clinical practice, such as pathologic and endoscopic diagnosis, and guidelines for treatment and surveillance.


Subject(s)
Adenoma , Carcinogenesis , Cellular Senescence , Colon , Colorectal Neoplasms , CpG Islands , Diagnosis , DNA Mismatch Repair , Genes, Tumor Suppressor , Methylation , Phenotype , Polyps , United Nations
17.
Article in English | WPRIM | ID: wpr-212864

ABSTRACT

OBJECTIVE: To evaluate the importance of Lynch syndrome associated risk screening in the patients aged less than 50 years affected from endometrial cancer. METHODS: From 2007 to 2014, 41 patients affected from endometrial cancer and aged less than 50 years underwent surgery at the Complex Operative Unit of Gynecology and Obstetrics, Cannizzaro Hospital of Catania, Italy. They were selected to undergo mismatch repair gene mutation analysis using immunohistochemistry (IHC; four markers: MLH1, MSH2, MSH6, PMS2) and microsatellite instability (MSI) test. For samples that resulted negative to IHC (abnormal finding), MSI test was performed to further study the suspected mutation. Samples were classified as MSI-high (MSI-H) if more than one marker was identified as unstable; MSI-low (MSI-L) if only one marker was identified as unstable; or MSI-stable (MSI-S) if no marker was identified as unstable. Samples were subdivided into two groups: MSI-H/L and MSI-S. Statistical analysis was performed to assess differences regarding survival, tumor staging, grading, and invasion of lymphovascular space between these two groups. RESULTS: IHC analysis showed that in 46% (19/41) of samples there was negative outcome. Forty-two percent (8/19) of these negative samples were unstable (either low or high). Of eight patients showing MSI, 75% were MSI-L, while 25% were MSI-H. Differences in survival, stage, grade, lymphovascular space invasion and Amsterdam criteria adherence were not statistically significant due to the small size of the cohort. CONCLUSION: IHC and MSI test results of our cohort lead us to assess the relevance of performing Lynch syndrome genetic screening in endometrial cancer patients aged less than 50 years at the time of diagnosis.


Subject(s)
Cohort Studies , Colorectal Neoplasms, Hereditary Nonpolyposis , Diagnosis , DNA Mismatch Repair , Endometrial Neoplasms , Female , Genetic Testing , Gynecology , Humans , Immunohistochemistry , Italy , Mass Screening , Microsatellite Instability , Neoplasm Staging , Obstetrics
18.
Article in Korean | WPRIM | ID: wpr-95359

ABSTRACT

Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common hereditary colorectal cancer syndrome and accounts for about 5% of colorectal cancer. It is inherited as autosomal dominant type and is caused by germline mutations in mismatch repair genes such as MLH1, MSH2, MSH6, and PMS2. Patients with HNPCC are characterized by a high level of microsatellite instability. They commonly develop colorectal cancer at young age and increase risk of extra-colic malignancies, especially endometrial cancer. They also show better oncologic outcomes compared to sporadic colorectal cancer. Several tools are used in diagnosis of HNPCC, including history taking, microsatellite instability test, immunohistochemistry for mismatch repair protein, and gene test. Affected patients and their families should get genetic counseling and regular surveillance for cancers, which can improve their survival rate.


Subject(s)
Colorectal Neoplasms , Colorectal Neoplasms, Hereditary Nonpolyposis , Diagnosis , DNA Mismatch Repair , Endometrial Neoplasms , Female , Genetic Counseling , Genetic Testing , Germ-Line Mutation , Humans , Immunohistochemistry , Microsatellite Instability , Survival Rate
19.
Article in English | WPRIM | ID: wpr-192005

ABSTRACT

The major risk factor for ovarian cancer (OC) is mutation of the BRCA1 or BRCA2 DNA mismatch repair genes, which occurs in approximately 10% of OC cases. Most previous studies have demonstrated that BRCA1- and BRCA2-mutated OCs are associated with better prognosis than sporadic OCs. However, information about the patterns and clinical course of the metastatic spread of BRCA-mutated OCs is limited. Herein, we describe a case of OC with a BRCA1 mutation and skin metastases in a 49-year-old patient, which to the best of our knowledge has not been reported previously.


Subject(s)
DNA Mismatch Repair , Humans , Middle Aged , Neoplasm Metastasis , Ovarian Neoplasms , Prognosis , Risk Factors , Skin
20.
Article in English | WPRIM | ID: wpr-26794

ABSTRACT

PURPOSE: Lynch syndrome, the commonest hereditary colorectal cancer syndrome, is caused by germline mutations in mismatch repair (MMR) genes. Three recently developed prediction models for MMR gene mutations based on family history and clinical features (MMRPredict, PREMM1,2,6, and MMRPro) have been validated only in Western countries. In this study, we propose validating these prediction models in the Korean population. MATERIALS AND METHODS: We collected MMR gene analysis data from 188 individuals in the Korean Hereditary Tumor Registry. The probability of gene mutation was calculated using three prediction models, and the overall diagnostic value of each model compared using receiver operator characteristic (ROC) curves and area under the ROC curve (AUC). Quantitative test characteristics were calculated at sensitivities of 90%, 95%, and 98%. RESULTS: Of the individuals analyzed, 101 satisfied Amsterdam criteria II, and 87 were suspected hereditary nonpolyposis colorectal cancer. MMR mutations were identified in 62 of the 188 subjects (33.0%). All three prediction models showed a poor predictive value of AUC (MMRPredict, 0.683; PREMM1,2,6, 0.709; MMRPro, 0.590). Within the range of acceptable sensitivity (> 90%), PREMM1,2,6 demonstrated higher specificity than the other models. CONCLUSION: In the Korean population, overall predictive values of the three models (MMRPredict, PREMM1,2,6, MMRPro) for MMR gene mutations are poor, compared with their performance in Western populations. A new prediction model is therefore required for the Korean population to detect MMR mutation carriers, reflecting ethnic differences in genotype-phenotype associations.


Subject(s)
Area Under Curve , Colorectal Neoplasms , Colorectal Neoplasms, Hereditary Nonpolyposis , DNA Mismatch Repair , Genetic Association Studies , Genetic Testing , Germ-Line Mutation , Humans , ROC Curve , Sensitivity and Specificity
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