Elderly patients with colorectal cancer have different clincopathological characteristics from younger patients. Colorectal cancers tend to localize in the proximal colon, from cecum to the splenic flexure in the elderly patients. Changes in the stools, rectal bleeding or black stool, abdominal pain, fatigue, weight loss and anemia are the common symptoms. Analysis showed that age is one of independent risk factors for lower completion rates of colonoscopy. Therefore, the choice of diagnosis methods in elderly patients should be careful. Achieving a clear diagnosis and avoiding complications should be considered at the same time. Most colorectal cancers in elderly are highly and moderately differentiated adenocarcinomas and locally advanced, and have less lymphatic and blood metastasis. The proportion of poorly differentiated adenocarcinoma increases with the increase of age, which should be concerned. Multiple colorectal cancers and colorectal cancer with extra-colorectal malignancy are not rare in the elderly patients. The common extra-colorectal tumors consist of gastric cancer, lung cancer, biliary carcinoma, pancreas cancer and malignancy from blood system. Molecular events, such as mutations of KARS, BRAF, TP53 and deficiency of DNA mismatch repair, are more frequent in elderly colorectal cancer patients. Many factors have impact on treatment decision in elderly patients with colorectal cancer, including age, comorbidities, physiological functions of organs and willingness of patients and their relatives. Although surgery is still the main treatment, the proportion of radical surgery is lower and emergency surgery is higher as compared to younger patients. With the development of minimally invasive surgical techniques and advances in anesthesia and perioperative management, laparoscopic surgery has become widespread in elderly patients with colorectal cancer. In addition, more attention should be paid to adjuvant therapy. Comprehensive individualized treatment plan should be taken to improve outcomes.
Adenocarcinoma ; pathology ; Aged ; Colonoscopy ; Colorectal Neoplasms ; diagnosis ; genetics ; pathology ; surgery ; Humans ; Laparoscopy ; Mutation ; Risk Factors

The molecular genetics of colorectal carcinomas are among the best understood of common human cancers. Three inter-related molecular pathways are involved. The chromosomal instability pathway begins with inactivation of the APC/beta-catenin genes followed by activation of oncogenes and inactivation of additional suppressor genes, commonly with high frequency of allelic losses, cytogenetic abnormalities. The microsatellite instability pathway begins with inactivating one of a group of genes responsible for DNA nucleotide mismatch repair leading to extensive mutations in both repetitive and non-repetitive DNA sequences with low frequencies of allelic losses and rare alteration of tumor DNA content. Finally, the CpG island methylation pathway involves inactivation of genes by methylation of cytosines in promoter regions to silence gene expression without DNA sequence alterations. Molecular genetics have the potential for clinical applications. Combination of genetic classification of high levels of microsatellite instability (MSI-H), gene expression analysis of mismatch repair genes and subsequent mutation analysis of inactivated genes can be used as an effective method for the identification of hereditary nonpolyposis colorectal carcinoma patients. Molecular genetic alterations have been proposed to be of prognostic value, including allelic deletion on chromosome 18q, and on chromosome 17p. MSI-H has been reported as a marker for better prognosis. Individualizing chemoradiation by use of predictive markers for response or resistance to therapy is important in patients with advanced disease or candidacy for adjuvant therapy.
Chromosomal Instability ; Colorectal Neoplasms/diagnosis/*genetics/pathology ; English Abstract ; Humans ; Microsatellite Repeats

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited disease associated with germ-line mutations in mismatch repair genes and microsatellite instability. This article reviews the molecular biology and clinical pathology of HNPCC.
Colorectal Neoplasms, Hereditary Nonpolyposis ; diagnosis ; genetics ; pathology ; DNA Mismatch Repair ; Humans ; Microsatellite Instability

OBJECTIVETo explore the prevalence, clinical features and prognosis of multiple primary neoplasms in patients with colorectal carcinoma (CRC).

METHODSData of colorectal cancer patients admitted to our hospital from June 1994 to June 2002 were analyzed retrospectively. Patients were divided into multiple-cancer group (MCG) and single- cancer group (SCG). Clinical features and prognosis were compared between two groups.

RESULTSThe incidence of multiple cancers was 7.4 % (83/ 1125). Forty- seven patients had multiple colorectal cancers metachronous CRC(S) in 12 and synchronous CRC(S) in 35. Thirty- six patients 5 patients with synchronous cancers had malignant tumors outside colorectal tract,12 of whom were gastric carcinomas. No significant differences were found between MCG and SCG regarding gender, onset age, Dukes stage and differentiation of index CRC. Cancer family history (P=0.002) and colorectal adenoma (P=0.036) were significantly more common in MCG than those in SCG. The local recurrence or distant metastasis in MCG was significantly higher than that in SCG (P=0.047), though there was no significant difference in survival between the two groups. Forty- one percent of index tumors were located in right colon in MCG, significantly higher than that in SCG (P=0.048). The secondary tumors were mainly adenoma cancerization in MCG.

CONCLUSIONCancer family history and colorectal adenoma seems to be at high risk for developing multiple cancers in CRC patients. Gastric cancer and colorectal adenoma cancerization were common secondary tumors of multiple primary neoplasms in patients with colorectal carcinoma.

Adenomatous Polyps ; genetics ; Adult ; Aged ; Colorectal Neoplasms ; diagnosis ; epidemiology ; pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Neoplasms, Multiple Primary ; diagnosis ; epidemiology ; pathology ; Prognosis ; Retrospective Studies ; Risk Factors

The extensive study of genetic alterations in colorectal cancer (CRC) has led to molecular diagnostics playing an increasingly important role in CRC diagnosis and treatment. Currently, it is believed that CRC is a consequence of the accumulation of both genetic and epigenetic genomic alterations. It is known that there are at least 3 major pathways that lead to colorectal carcinogenesis: (1) the chromosomal instability pathway, (2) the microsatellite instability pathway, and (3) the cytosine-phospho-guanine island methylator phenotype pathway. With recent advances in CRC genetics, the identification of specific molecular alterations responsible for CRC pathogenesis has directly influences clinical care. Patients at high risk for developing CRC can be identified by genetic testing for specific molecular alterations, and the use of molecular biomarkers for predictive and prognostic purposes is also increasing. This is clearly supported by the recent advances in genetic testing for CRC whereby specific molecular alterations are identified for the purpose of guiding treatment with targeting therapies such as anti-endothelial growth factor receptor monoclonal antibodies.
Antibodies, Monoclonal ; Biomarkers ; Carcinogenesis ; Chromosomal Instability ; Colorectal Neoplasms* ; Diagnosis ; Epigenomics ; Genetic Testing ; Genetics* ; Humans ; Microsatellite Instability ; Pathology, Molecular ; Phenotype

OBJECTIVETo explore the value of detection of adenomatous polyposis coli (APC) gene and K-ras gene mutations in fecal and blood samples in colorectal neoplasm screening.

METHODSFrom 84 subjects undergoing colonoscopic examination (including 31 with colorectal carcinoma, 26 with colorectal adenoma, and 27 healthy subjects) between October, 2003 and March, 2004, 5 ml of heparinized peripheral blood and 3-5 g fecal specimens were collected. The DNA was extracted from the specimens for detecting the mutation of APC and K-ras gene using polymerase chain reaction-single strand conformation polymorphism and the results were analyzed statistically.

RESULTS AND CONCLUSION(1) The incidence of APC gene mutation was 41.9% and 57.7% in the plasma, and 34.8% and 26.8% in the fecal specimens of colorectal carcinoma patients and adenoma patients, respectively, both higher than that in normal subjects (P<0.05), suggesting high consistency between fecal and plasma APC gene mutation detection (K=0.811, P<0.05). (2) The incidence of plasma K-ras mutation was 48.4% in colorectal carcinoma patients, 3.8% in adenoma patients and 0% in normal control subjects, and in the feces, the incidences were 54.8%, 7.7% and 11.1%, respectively. The mutation rate was higher in carcinoma patients than in adenoma patients and normal subjects (P<0.05). Fecal K-ras gene mutation detection was consistent with plasma detection (K=0.662, P=0.000). (3) APC gene mutation detection showed a low sensitivity and specificity in the diagnosis of colorectal carcinoma, but K-ras mutation detection showed a high specificity. The diagnostic sensitivity increased when combining APC and K-ras gene detection in the plasma or fecal specimens, but there was no evidence to suggest that APC and K-ras mutation detection in the plasma could be better than detection in the feces. (4) For colorectal carcinoma, APC gene mutation is associated with lymphoid node metastasis, but not with the patient's gender, age, tumor location, differentiation, distant organ metastasis or CEA level (P>0.05), and the mutation of K-ras gene is related to the degree of tumor differentiation.

Adenomatous Polyposis Coli ; blood ; genetics ; Case-Control Studies ; Colorectal Neoplasms ; blood ; diagnosis ; genetics ; pathology ; DNA ; blood ; Feces ; Female ; Genes, ras ; genetics ; Humans ; Male ; Middle Aged ; Mutation

OBJECTIVETo investigate the expression of connective tissue growth factor (CTGF) in colorectal cancer(CRC) and its association with clinicopathologic parameters and overall survival rate.

METHODSFresh tumor tissues and matched distal normal colon tissues were collected from 92 patients diagnosed as CRC by surgical operation. The expression level of CTGF mRNA was quantified by quantitative reverse transcription PCR. Thirty out of 92 pairs of tissue specimens were selected randomly to detect CTGF protein by immunohistochemistry. All the cases were followed up to identify prognostic factors for survival.

RESULTSCTGF mRNA expression was up-regulated in CRC. The positive rate of CTGF protein expression tissues (73.3%) was significantly higher than that in the corresponding normal tissues (23.3%, P<0.01). CTGF expression was lower in patients with lymphatic metastasis or stage III/IIII disease (all P<0.05). A negative association was also observed between the CTGF protein positive rate and tumor infiltration depth (P<0.05). The relative expression of CTGF mRNA in tumor tissues was classified into high and low expression groups. The 5-year cumulative survival rate was lower in patients with low CTGF expression (29.3%) as compared to those with high CTGF expressions (68.3%) (P<0.01). Cox regression analysis revealed that the relative expression level of CTGF was independent factor of overall survival (RR=2.960, 95%CI:1.491-1.587, P<0.01). ROC curve analysis showed that sensitivity and specificity of CTGF mRNA expression for prediction of 5-year survival were 64.9% and 74.5%, respectively.

CONCLUSIONSThe aberrant expression of CTGF is associated with the malignant biological behaviors of CRC. Low expression of CTGF is associated with worse prognosis of CRC.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; diagnosis ; metabolism ; pathology ; Connective Tissue Growth Factor ; genetics ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; RNA, Messenger ; genetics

OBJECTIVE: To explore the clinicopathologic and molecular characteristics of hereditary nonpolyposis colorectal cancer (HNPCC), and to improve the level of diagnosis and treatments of HNPCC. METHODS: Thirty HNPCC patients (HNPCC group) who were treated in Xiangya Hospital were retrospectively analyzed, and 25 patients with sporadic colorectal cancer in the same duration were randomly chosen as a control group. The onset of age, location of tumor, pathological type, treatment method, and prognosis were compared in the 2 groups. The expression loss rate of mismatch repair gene (MMR) MLH1 and MSH2 in the 2 groups was detected by immunohistochemistry. RESULTS: The onset age in the HNPCC group was earlier than that in the control group (P<0.05). The rate of proximal colonic tumor the occurrence of multiple tumors, and the proportion of well differentiated adenocarcinoma in the HNPCC group were all higher than those in the control group (P<0.05). The expression loss rate of MLH1 and MSH2 in the HNPCC group was higher than that in the control group (P<0.05). One third in the HNPCC group received subtotal proctocolectomy. The prognosis of HNPCC patients was comparable with that of patients with sporadic colorectal cancer (P>0.05). CONCLUSION HNPCC patients are characterized with early onset associating with multiple tumors. The accuracy of diagnosis can be improved by combining the detection of MMR gene. Optimal surgical treatment and close follow-up may bring good result to HNPCC patients.
Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Adenocarcinoma ; diagnosis ; genetics ; pathology ; surgery ; Aged ; Case-Control Studies ; Colorectal Neoplasms, Hereditary Nonpolyposis ; diagnosis ; genetics ; pathology ; surgery ; Endometrial Neoplasms ; pathology ; Female ; Humans ; Male ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; genetics ; metabolism ; Mutation ; Neoplasms, Second Primary ; pathology ; Nuclear Proteins ; genetics ; metabolism ; Retrospective Studies

The aim of the present study was to accurately evaluate the association of Sox2 expression with the survival of patients with digestive tract cancers. Relevant literatures were identified by comprehensively searching databases including the Pubmed, Embase, CBMdisc, and Wanfang (up to October 2014). A meta-analysis was performed to clarify the association between Sox2 expression and overall survival or clinicopathological parameters of patients with digestive tract cancers (esophageal, gastric, and colorectal cancers). The results showed a significant association between high Sox2 expression and poor overall survival in patients with digestive tract carcinomas (HR=1.55, 95% CI=1.04-2.31), especially for patients with esophageal cancer (HR=2.04, 95%CI=1.30-3.22), colorectal cancer (HR=1.40, 95% CI=1.04-1.89), and digestive tract adenocarcinoma (HR=1.80, 95% CI=1.12-2.89), for Europeans (HR=1.98, 95% CI=1.44-2.71) or patients who did not receive neoadjuvant treatment (HR=1.73, 95% CI=1.10-2.72). Furthermore, Sox2 over-expression was highly correlated with vascular invasion (OR=1.86, 95% CI=1.25-2.77) and poor differentiation (OR=1.88, 95% CI=1.14-3.08), especially in esophageal and colorectal cancers. In conclusion, Sox2 expression may serve as a novel prognostic factor for patients with digestive tract cancers. Over-expression of Sox2 that is correlated with vascular invasion and poor differentiation suggests poor outcomes of patients with digestive tract cancers.
Antineoplastic Agents ; therapeutic use ; Biomarkers, Tumor ; genetics ; metabolism ; Colorectal Neoplasms ; diagnosis ; drug therapy ; mortality ; pathology ; Esophageal Neoplasms ; diagnosis ; drug therapy ; mortality ; pathology ; Gastrointestinal Tract ; metabolism ; pathology ; Gene Expression ; Humans ; Neoadjuvant Therapy ; methods ; Neoplasm Grading ; Neoplasms, Vascular Tissue ; diagnosis ; drug therapy ; mortality ; secondary ; Prognosis ; SOXB1 Transcription Factors ; genetics ; metabolism ; Stomach Neoplasms ; diagnosis ; drug therapy ; mortality ; pathology ; Survival Analysis

Adenomatous Polyposis Coli ; genetics ; pathology ; Colonic Neoplasms ; classification ; genetics ; pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis ; diagnosis ; genetics ; DNA Glycosylases ; metabolism ; Humans ; Intestinal Polyps ; pathology ; Lymphatic Metastasis ; Neoplasm Staging ; Neuroendocrine Tumors ; classification ; pathology ; Precancerous Conditions ; pathology ; Rectal Neoplasms ; classification ; genetics ; pathology ; World Health Organization