The association between postmenopausal osteoporosis and APC gene polymorphism was analyzed based on quantitative CT measurement of lumbar vertebral bone density / 中华内分泌外科杂志

Objective:To investigate the relation of two SNPs of adenomatous polyposis coli (APC) gene E1317Q (RS1801166, G > C) and D1822V (RS45952, A > T) polymorphism with osteoporosis and bone metabolism in postmenopausal women.Methods:A total of 374 postmenopausal women who underwent routine physical examination in the Second Affiliated Hospital of Zhejiang University School of Medicine from Mar. 2019 to Mar. 2021 were selected as subjects, and divided into normal bone mass group (103 cases) , osteoparrosia group (114 cases) and osteoporosis group (157 cases) . Bone mineral density was measured by a 128-slice spiral CT machine manufactured by Siemens. Clinical and bone metabolic indicators were recorded. Two SNPs were genotyped by capillary electrophoresis and fragment analysis (SNaPshot) . The relative expression level of APC gene mRNA was measured in quantitative real-time fluorescence quantitative polymerase chain reaction system.Results:There were significant differences in genotype and allele frequency distribution of APC rs1801166 and RS45952 among the three groups (all P<0.05) . For rs1801166 site, paircomparison results showed that the genotype distribution of the osteoporosis group was significantly different from that of the normal bone mass group and the decreased bone mass group ( P<0.05) . Allele frequency was significantly different between the two groups ( P<0.05) . For rs45952 site, pairwise comparison showed that the genotype distribution and allele frequency were significantly different between the osteoporosis group and the normal bone mass group ( P<0.05) . There were statistically significant differences in serum calcium, serum phosphorus, alkaline phosphatase, 25-hydroxyvitamin and bone mineral density between wild type and mutant type at rs1801166 (all P<0.05) . There were statistically significant differences in serum calcium, alkaline phosphatase, 25-hydroxyvitamin and bone mineral density between wild type and mutant at RS45952 site (all P<0.05) . There was statistical significance in the mRNA relative expression of APC gene in the normal bone mass group, the bone mass reduction group and the osteoporosis group ( P<0.05) . The mRNA relative expression level of APC gene in wild type at rs1801166 and RS45952 sites was significantly higher than that in mutant type (all P<0.05) . Conclusion:APC gene polymorphism is significantly correlated with osteoporosis and bone metabolism in postmenopausal women, and may affect the expression level of APC gene.

A Novel Adenomatous Polyposis Coli Gene Mutation of Cribriform-Morular Variant Papillary Thyroid Carcinoma: A Case Report / 대한이비인후과학회지

Cribriform-morular variant papillary thyroid carcinoma (CMV-PTC) is a rare cancer that may arise in patients with familial adenomatous polyposis (FAP). Adenomatous polyposis coli (APC) gene mutation is associated with FAP, which is known as a premalignant lesion of colon cancer. In this report, we report a 16 years old patient of CMV-PTC comorbid with FAP, which was related with a new type of APC gene mutation.

Evaluation of the Combination of APC and DCC Gene Methylation in the Early Diagnosis of Lung Cancer / 现代检验医学杂志

Objective To investigate the significanceof both the adenomatous polyposis coli (APC)and deleted in colorectal carcinoma (DCC)gene methylation in the early diagnosis of lung cancer.Methods 245 patients with lung cancer and 150 patients with non-malignant lung disease patients and 40 healthy volunteers were drawn for the experiment.A methylation specific PCR (MSP)was used to detect the methylation status of APC and DCC in the peripheral blood.Results The posi-tive rates of APC and DCC genes promoter methylation Peripheral blood of patients with lung cancer were 26.53% (65/245)and 36.33% (89/245),respectively.The positive rates of APC and DCC genes promoter methylation Peripheral blood of patients with benign lung diseases were 2.67% (4/150),8.00%(12/150),respectively.The positive rates of APC and DCC genes promoter methylation Peripheral blood of healthy volunteers were 0.There was a significant difference between patients with the lung cancer,those with the benign lung diseases and Healthy volunteers (P 0.05).There was no correlation between methylation test results and pa-tient gender,age,pathological type,pathological grade,TNM stage and so on (P >0.05).Conclusion APC and DCC gene methylation were closely related to the development of non-small cell lung cancer.They can be used as an early diagnostic marker of lung cancer.

APC protein immunoexpression in colorectal adenoma and adenocarcinoma / Imunoexpressão da proteína APC nos tecidos de adenoma e de adenocarcinoma colorretais

BACKGROUND: activation of the Wnt pathway by mutated APC gene is considered the initial event in colorectal carcinogenesis. The identification of these mutations can improve the specific treatment of the adenocarcinoma. OBJECTIVE: detect and evaluate wild-type APC protein in tissue from colorectal adenoma, adenocarcinoma and adjacent mucosa. METHODS: 42 patients that underwent surgery for adenocarcinoma and 53 patients with resected adenomas were studied. Tissue samples from the adenocarcinoma were obtained from the tumor and from adjacent non-neoplastic mucosa located 10 cm from the proximal margin of the tumor. Adenoma tissue was obtained from representative areas. Blocks of tissue microarray (TMA) were submitted to immunohistochemistry with anti-APC, with readings of positivity and intensity of immunostaining and the score of immune expression of APC protein was obtained. RESULTS: the APC protein immune expression score showed a significantly lower expression of APC protein in the adenoma when compared with the adenocarcinoma (p < 0.0001) and adjacent mucosa (p < 0.0001). The APC protein immune expression score in the colorectal mucosa and adjacent to the adenocarcinoma showed no significant difference (p = 0.24). CONCLUSIONS: the finding of decreased expression of APC protein in adenoma tissue may indicate that the mutated APC gene may contribute to the changes in the adenoma-carcinoma process of carcinogenesis sequence. The strong expression of protein APC in tissues from the carcinoma and adjacent mucosa suggests that in most patients in this series, the mutation of the APC gene did not participate in the oncogenesis mechanism. (AU)

RACIONAL: a ativação da via Wnt pelo gene APC mutado é considerado evento inicial da carcinogênese colorretal. A identificação dessas mutações pode tornar o tratamento do adenocarcinoma mais específico. OBJETIVO: detectar e avaliar a proteína APC não mutada em tecidos de adenoma, adenocarcinoma e mucosa adjacente. MÉTODO: estudados 42 doentes operados de adenocarcinoma e 53 com adenomas ressecados. Tecidos de adenocarcinoma foram obtidas da neoplasia e da mucosa adjacente não neoplásica situadas a 10 cm da margem proximal do tumor. Tecidos do adenoma foram obtidas de área representativa. Blocos de tissue microarray (TMA) foram submetidos a imuno-histoquímica com anticorpo anti-APC. Avaliadas a positividade e intensidade da expressão e obtidos escores da imunoexpressão da proteína APC. RESULTADOS: o escore da imunoexpressão da proteína APC no adenoma foi significantemente menor do que no adenocarcinoma (p < 0,0001) e na mucosa adjacente (p < 0,0001). O escore da imunoexpressão da proteína APC na mucosa adjacente e no adenocarcinoma não mostraram diferença significante (p = 0,24). CONCLUSÕES: a menor expressão da proteína APC no adenoma pode indicar que o gene APC mutado participa das alterações do processo adenoma-carcinoma. A forte expressão da proteína APC no CCR e na mucosa adjacente sugerem que a mutação do gene APC não participou da oncogênese. (AU)

Cáncer de tiroides y síndromes polipósicos intestinales Síndrome de Gardner / Thyroid cancer and intestinal polyposis syndromes Gardner syndrome

Resumen Presentamos el caso de una mujer de 22 años de edad, evaluada debido a que en su historia familiar a su madre se le encontró carcinoma de colon sigmoide. A la paciente se le diagnosticó poliposis colónica, que resolvió tras remoción endoscópica de las lesiones. Se realizó estudio de nódulo tiroideo y se realizó tiroidectomía total encontrándose un carcinoma papilar de tiroides como diagnóstico definitivo. Hicimos una revisión de la literatura. (Acta Med Colomb 2013; 38: 182-185).

Abstract We report the case of a 22-year-old woman evaluated because in her family history his mother had a sigmoid colon carcinoma. The patient was diagnosed with colonic polyposis, which resolved after endoscopic removal of the lesions. We made the study of a thyroid nodule and performed total finding a papillary thyroid carcinoma as definitive diagnosis. (Acta Med Colomb 2013; 38: 182-185).

Detection of truncating mutations of APC gene by digital protein truncation test labeled with fluorescent Lys-t-RNA / 中华消化外科杂志

Objective To investigate the relationship between truncating mutations of APC gene and sporadic colorectal cancer,and analyze the feasibility of non-radioactive protein truncation test (PTT) in the detection of mutations of APC gene.Methods Ninety-six samples of sporadic colorectal cancer tissues ( including 44 patients with colonic cancer and 52 patients with rectal cancer) were obtained from the General Hospital of Ningxia Medical University from September 2008 to September 2010.The mutation cluster region of the APC gene was screened using digital PTT labeled with fluorescent Lys-t-RNA,with a polymerase chain reaction fragment amplified from genomic DNA serving as a tenplate for in vitro translation.The occurrence of gene mutation was determined according to the emergence of truncated peptides.The mutation cluster region of the APC gene in 46 samples of colorectal cancer tissues was analyzed by direct sequencing.The detection rates of the 2 methods were compared by chi-square test.Results Thirteen (26％) truncated peptides were detected in the 50 samples of colorectal cancer tissues.The mutation type of 4 samples is nonsense mutation,which resulted in emergence of truncated gene products.Eleven (24％) truncated peptides were detected in the 46 samples of colorectal cancer tissues.There was no significant difference in the detection rates between PTT and direct sequencing ( x2 =0.033,P ＞ 0.05 ).Conclusions Truncating mutations of APC gene are common alterations in sporadic colorectal cancer in the Chinese.Digital PTT labeled with fluorescent Lys-t-RNA is rapid and high-sensitive in screening gene mutations.

Benefits from genetic test in descendants of familial adenomatous polyposis syndrome: report of a family in southern Thailand.

Background: Familial adenomatous polyposis (FAP) is an inherited colorectal cancer predisposing syndrome that has an autosomal dominant mode of inheritance with complete penetrance. Although the disease-causing gene of FAP, the adenomatous polyposis coli (APC) gene, is well understood, genetic testing for FAP remains uncommon in Thailand, possibly because of its high cost. Objective: Present a family in southern Thailand that had benefited from this test. Subject and methods: The proband was a 31-year-old man who had rectal cancer with profuse adenomatous polyposis of his colon. Results: APC mutation screening revealed a novel mutation at codon 1249 (TGC1249TAA) that could predict a premature stop codon. On screening of three siblings in the same generation who were alive and 11 members of the descendant generation, four cases were positive for the mutation. The positive members were confirmed to have a type of diffuse colonic polyposis by endoscopy, and a prophylactic colectomy was performed without complications for every affected individual. Conclusion: A genetic test is cost-effective. It should be considered for FAP, especially when the number of at-risk family members is high.

APC Mutation Spectra in Sporadic Colon Cancer Tissue among Korean

PURPOSE: APC (adenomatous polyposis coli) gene is one of the tumor-suppressor genes that acts in the early stages of cancer. Among general colon cancer patients, normal APC gene expression is deficient in 80%. It seems that APC is the most important gene in the development of colon cancer. This study was performed to analyze the mutation spectra of APC gene in sporadic colon cancer tissue from Korean patients with colon cancer. METHODS: A total of 38 patients with sporadic colon cancer were enrolled. Colon cancer tissues were analyzed for the determination of APC gene mutation spectra by multiplex ligation-dependent probe amplification (MLPA) method using SALSA MLPA P403 APC kit (MRC-Holland, Amsterdam, NL). RESULTS: APC gene mutations showing deletion/duplication in one or more exons were detected in 23 (60.5%) patients. Duplication in 13 patients (56.5%), duplication and deletion in 7 patients (30.4%), and deletion in 3 patients (13.1%) was detected. The incidence of APC gene mutation found in this study was highest in exon 3. From this study, no significant differences were observed with respect to clinicopathologic findings and the presence or absence of APC mutations. CONCLUSION: The frequency of APC gene mutation was about 61% in Korean patients with colon cancer, it showed concordance with the previous reports on the frequency of APC gene mutation from Caucasian patients with sporadic colon cancer. However, in contrast to these reports, the frequency of duplication disclosed much higher than those of western countries.

Promoter methylation of APC genes in cervical cancer: correlation with clinicopathologic characteristics / 中国癌症杂志

Background and purpose: The Writ cell-signaling pathway is the key cellular developmental pathway. Dysregulation of this pathway has been implicated in the initiation and progression of cancer. Adenomatous polyposis coli (APC) is an important tumor suppressor gene of the Writ signaling pathway. The methylation of APC promoter and the accompanying loss of the APC transcript have been shown to occur in a significant proportion of cancers. However, there are few reports on the relationship between cervical cancer and methylation of APC. This study was aimed to investigate the promoter methylation status of the APC genes in cervical cancer and its correlation between clinicopathologic characteristics and the infection of high-risk HPV DNA. Methods: Promoter methylation was evaluated using a MSP (methylation-specific polymerase chain reaction) in 95 cervical cancer tissue specimens and 20 normal controls. The relationship between clinicopathologic parameters and the methylation status was evaluated. Results: The frequencies of promoter methylation of APC in cervical cancer were 56.8%. Cervical cancer had significant higher methylation frequencies than that of the controls (10%, P<0.01). The result showed that the methylation analysis of APC promoter and high-risk HPV DNA testing had good consistency (Kappa=0.348, P<0.001). The promoter methylation of APC was significantly higher in adenocarcinoma (AC) than in squamous cell carcinoma (SCC) (74.1% vs 50.0%, respectively, P<0.05). The larger tumor size, positive lymph node metastasis and positive HPV DNA exhibited an increased promoter methylation frequency for APC (P<0.05). There were no significant associations between the methylation frequencies for APC gene to age, invasion depth, FIGO stage and histological grade. Conclusion: Our results suggested that the promoter methyiation of APC and high-risk HPV DNA testing had good consistency. APC gene promoter methylation was a frequent epigenetic event in cervical carcinoma and had a significant correlation with cancer pathological types.

Clinical Analysis for 30 Cases of Total or Subtotal Abdominal Colectomy and Total Proctocolectomy

PURPOSE: A total or a subtotal abdominal colectomy and a total proctocolectomy are performed occasionally for the surgical treatment of familial adenomatous polyposis, multiple colorectal cancers, ulcerative colitis, acute lower GI bleeding, and malignancy other than colorectal cancer. We studied 30 cases of patients who received either a total or a subtotal abdominal colectomy and a total proctocolectomy in one of the three hospitals affiliated with the Catholic University between January 1990 and December 2001. Our goal was to determine whether the total or subtotal abdominal colectomy and the total proctocolectomy are difficult and complicated procedures by comparing the mortality, the morbidity, the survival rate, and the complications to previously considered and reported results. METHODS: Thirty patients treated with either total or subtotal abdominal colectomy and with a total proctocolectomy from January 1990 to December 2001 were chosen for this study. Their gender, age, underlying diseases, family history, hospital days, symptoms, changes in defecation habits following the procedure, complications, mortality, survival rate, and relationship to malignancy were evaluated. RESULTS: Of the patients who received either total or subtotal abdominal colectomy and a total proctocolectomy, the average age was 44.6 years, the gender ratio was 1:1, and the underlying diseases were familial adenomatous polyposis (FAP) (43%), ulcerative colitis (UC) (20%), multiple colorectal cancers (17%), stomach cancer (7%), and Crohn's disease (3%). Diarrhea and rectal bleeding were the most common clinical symptoms, and abdominal pain and intestinal obstruction were frequently observed. A total proctocolectomy (TPC) with permanent ileostomy was the most frequently performed procedure (47%), and a TPC with ileoanal anastomosis was done in 10% of the cases. A total abdominal colectomy (TAC) with ileorectal anastomosis was applied in 23% of the cases, and subtotal abdominal colectomy (sTAC) with ileosigmoidal anastomosis was done in 20% of the cases. The operative mortality rate was 3% as one patient among thirty died. Postoperative complications developed in 33% of the patients. FAP and UC patients without cancer (45%) survived for over 4 or 5 years, but FAP and UC patients with cancer, especially an adenocarcinoma, survived for only 2.5 years. CONCLUSIONS: A total or subtotal abdominal colectomy (TAC or sTAC) and a total proctocolectomy (TPC) are appropriate procedures with low mortality, low morbidity, and a low complication rate for several kinds of diseases. A TPC with ileorectal anastomosis is the procedure of choice for sparing the rectum in FAP and UC patients without coexisting cancer and without mutation of the APC gene after codon 1250, but a TPC with ileoanal anastomosis is recommended if there is a mutation of the APC gene after codon 1250. A TPC with ileostomy is the preferred method for FAP and UC patients with coexisting cancer.

A Case of Thyroid Papillary Cancer Associated with Familial Adenomatous Polyposis / 대한내분비학회지

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome, typically characterized by multiple colorectal adenomas and increased incidence of colorectal carcinomas if left untreated. It is caused by germline mutations of the adenomatous polyposis coli (APC) gene, which has been mapped on chromosome 5q21, and is accompanied by various benign and malignant extracolonic manifestations. The prevalence of thyroid tumors developing in patients with FAP is about 1~2%, are associated with FAP and have certain characteristics; mean age of tumor diagnosis at less than 30 years of age, the pathology is the papillary histiotype in more than 90% of cases, including a so-called cribriform- morular pattern, and multifocality is a frequent feature. In a genetic analysis, thyroid cancer in FAP usually has a mutation in the 5-portion of exon 15 between 778 and 1309, on chromosome 5q21. Also, the ret/PTC (especially ret/PTC1 and ret/PTC3) and p53 genes are thought probably to be associated with thyroid cancer in FAP patients. A case of familial adenomatous polyposis, accompanied by thyroid papillary cancer, was experienced in a 29 year-old female. She had hundreds of adenomas throughout the entire colon and congenital hypertrophy of the retinal pigment epithelium (CHRPE). The pathological finding of thyroid cancer was revealed as a mixture of cribriform, trabecular and papillary patterns. In a genetic analysis, she and her brother had a germline mutation of the APC gene at codon 1309. In Korea, there has been no previous case of cribriform-morular pattern and familial genetic analysis in FAP associated with thyroid cancer. Therefore, this case is reported, with a review of the literature

Loss of Heterozygosity Affecting the APC and p53 Tumor Suppressor Gene Loci in Colorectal Cancers and Its Prognostic Significance

Development of the human colorectal cancer is associated with several distinct genetic abnormalities involving both dominant-acting oncogenes (K-ras, c-src) and tumor suppressor genes (APC, DCC, p53) which undergo inactivation or loss. In colorectal tumors, the common molecular alteration is localized in the 17p13 and 5q21 loci encoding the p53 and the APC gene, respectively. The identification of these genes may help the understanding of the pathogenesis of colorectal neoplasia. In order to determine whether the frequency of the genetic alterations varies with sex, age, tumor size, or site, including pathologic parameters, such as degree of differentiation, tumor stage, mucin component, lymphoid reaction, tumor invasion pattern, vein and nerve invasion, lymph node metastasis, and other parameters, such as disease-free survival, distant metastasis and patient outcome, the authors analyzed the loss of heterozygosity (LOH) of the APC and the p53 genes in paraffin-embedded specimens of 48 colorectal cancers by use of the polymerase chain reaction and restriction fragment length polymorphism. The results were as follows: the LOH affecting the APC was found in 15 out of 31 (48.4%) heterozygous patients, while the LOH of the p53 locus was observed in 11 out of 26 (42.3%) patients. Among 48 patients, the LOH at both the APC and the p53 loci was observed in five (10.4%) patient. No statistically significant associations were found between the LOH of the APC gene and the proposed parameters. The relationship between the LOH of the p53 and the histologic differentiation, lymphoid reaction was significant (P<0.05), but survival was not correlated. Statistically significant associations were found between overall survival of the colorectal cancer patients and distant metastasis, Astler-Coller stage, lymphoid reaction, invasion pattern, nerve invasion, vein invasion, lymph node metastasis, and disease free survival. The above results suggest that the LOH of the p53 genes could be involved in the progression of colorectal cancers. However, neither the LOH of the APC nor that of the p53 have significant association with survival of the colorectal cancer patients.

ABNORMAL CHANGE OF p53 GENE IN GASTRIC CANCER AND PRECANCER- OUS LESIONS AND APC GENE IN GASTRIC CARCINOMA AND NEAR TISSUES / 中华消化内镜杂志

p53 gene mutation (exon4 , 5 , 6 . 7 . 8 and intron6) in gastric cancer and precancerous le- sions and p53 gene (exon4 and intron6) .APC gene deletion in gastric carcinomas were studied by PCR/ SSCP and PCR/RFLP. Results showed: mutation rate of p53 in intestinal metaplasia ,dysplasia and gas- tric carcinoma was 37. 5% (3/8) ,42. 1 % (8/19) , 53. 3% (16/30) ,respectively. There was significant dif- ference between groups of metaplasia、dysplasia、cancer and that of normal control. We found there were no exon8 mutation in metaplasia and dysplasia , but 4 cases in cancer group. lt is suggestted that exon8 mutation occurs at the late stage of gastric cancer , but exon 5 , 6 , 7 mutation occur in the course of pre- cancerous lesions to cancer. Loss of heterozygosity (LOH) of exon4 . intron6 . APC was 47. 4 % ( 9/19) . 8. 7%C2/23).16. 7%(3/18) ,respectively. There are some relationship between LOH of exon4 and poor- ly differentiation , lymph node metastas , depth of invasion. LOH of exon4 may be one of prognostic marker of gastric cancer. We concluded that p53 gene mutation is an early event and perhaps has syner- gism with ras oncogene in gastric carcinogenesis

Mutation of Adenomatous Polyposis Coli Gene in Human Stomach Cancer

Recently the adenomaatous polyposis coli(APC) gene, a tumor suppressor gene, was identified and the cDNA was cloned from chromosome 5q21. Allelic deletion or point mutation of tumor suppressor genes(TSGs) has been considered as an important mechanism in development of human tumor. Point mutations affecting APC gene are seen in the hereditary syndrome, adenomatous polyposis and spordic colon cancer. However, the mutation of APC gene and other TSGs have not been described in gastric cancer. In order to identify the mutation of exon 11 of APC gene for gastric cancer, we amplified DNA extracted from paraffin-embedded tissues by polymerase chain reaction(PCR) and digested the PCR products with restriction enzyme Rsa I. We examined the DNA extracted from paraffin-embedded 44 gastric cancer tissues with lymph nodes. Eighteen(41%) among 44 were informative for the study exon 11 of the APC gene, and we found loss of heterozygosity(LOH) for APC in 6/18(33.3%). These data suggest that the point mutation or the base change of APC gene commonly occurs in gastric cancer. We conclude that the mutation of APC gene is strongly connected with development of human gastric cancer.