PURPOSE: The characteristic expression of DNA damage response proteins in familial breast cancers with BRCA1, BRCA2, or non-BRCA1/2 mutations has not been analyzed in Chinese patients. Our study aimed to assess the differential expression of microcephalin 1 (BRIT1), ATM serine/threonine kinase (ATM), checkpoint kinase 2 (CHEK2), BRCA1, RAD51 recombinase (RAD51), and poly (ADP-ribose) polymerase 1 (PARP-1) and establish the profile of Chinese familial breast cancers with different mutation status. METHODS: We constructed five tissue microarrays from 183 familial breast cancer patients (31 with BRCA1 mutations; 14 with BRCA2 mutations, and 138 with non-BRCA1/2 mutations). The DNA response and repair markers used for immunohistochemistry analysis included BRIT1, ATM, CHEK2, BRCA1, RAD51, and PARP-1. The expressions of these proteins were analyzed in BRCA1/2 mutated tumors. The association between pathologic characteristics with BRCA1/2 mutation status was also analyzed. RESULTS: In familial breast cancer patients, BRCA1 mutated tumors were more frequent with high nuclear grade, estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, low Ki-67, and positive CK5/6. BRCA1 mutated tumors had lower CHEK2 and higher cytoplasmic BRIT1 expression than BRCA2 and non-BRCA1/2 mutation tumors. BRCA2-associated tumors showed higher CHEK2 and cytoplasmic RAD51 expression than those in other groups. Nuclear PARP-1 expression in BRCA1/2-associated tumors was significantly higher than in non-BRCA1/2 mutation tumors. Moreover, we found quite a few of negative PARP-1 expression cases in BRCA1/2 mutated groups. CONCLUSION: The clinicopathologic findings of BRCA1-associated Chinese familial breast cancers were similar to the results of other studies. Chinese familial breast cancer patients with BRCA1/2 mutations might have distinctive expression of different DNA damage response proteins. The reduced expression of PARP-1 in Chinese BRCA1/2 mutated breast cancer patients could influence the therapeutic outcome of PARP-1 inhibitors.
Asian Continental Ancestry Group* ; Breast Neoplasms* ; Breast* ; Checkpoint Kinase 2 ; Cytoplasm ; DNA Damage* ; DNA Repair ; DNA* ; Estrogens ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Immunohistochemistry ; Phosphotransferases ; Rad51 Recombinase ; Receptor, Epidermal Growth Factor

Objective To analyze the status of biobanks in public hospitals in Shanghai.Methods A questionnaire survey on biobanks was conducted in 9 representative public hospitals in Shanghai.Results The management system of hospital biobanks in Shanghai was basically shaped,but the human resources and financial inputs were in shortage,and some management and regulations were not in place yet.Conclusions The biobanks of public hospitals need more inputs,improvement,and standardized management.

OBJECTIVETo study the morphologic and immunohistochemical features of gastrointestinal stromal tumors (GISTs) and to explore the reference parameters for malignancy.

METHODSSeventy six (76) cases of primary GISTs were distinguished from a group of gastrointestinal mesenchymal tumors by use of a panel of antibodies such as CD117, CD34 by immunohistochemical EnVision method, their biologic behaviors were analyzed by including their follow-up data.

RESULTSAll patients were adults, age range 32 to 81 years (mean 54 year), male 39 cases and female 37 cases; the tumors were situated in stomach (36 cases), in small intestine (23 cases), colon (2 cases) and rectum (15 cases). The most common symptoms were abdomen mass, vague pain and GI bleeding. Forty eight (48) cases were mainly located within the muscularis propria, 25 cases outside the serosa, and 3 cases below the mucosa. Grossly, they were of soft consistency often with hemorrhage, cystification or necrosis. Microscopically, the tumors were composed of spindle cells (46 cases) or epithelioid cells (9 cases) and of both cells (21 cases), arranged in interlacing fasicles, diffusing sheets, pallisading, whirling, alveolar and giant pseudo-rosette shapes. Tumor cells often had abundant cytoplasm with light to moderate eosinophilic or slight basophilic in staining, the nuclei generally showed spindle, blunted ends, round or signet in shape with nucleoli. Immunohistochemically, CD117 and CD34 showed diffuse strong expression, the positive rates were 98.7% and 68.4% respectively, alpha-SMA, MSA, S-100, PGP9.5 showed focal expression, the positive rates were 25.0%, 19.7%, 23.7% and 17.1% respectively, vimentin were all positive and desmin, GFAP, NF were all negative. Nine cases were benign, 19 cases borderline and 48 cases malignant. Follow-up of 20 cases with benign and borderline tumors found patients alive without tumor. In the malignant group of 34 cases, 10 cases were alive without tumor, 10 cases developed recurrence or metastasis, and 14 cases died of tumor. Coagulative necrosis, mitotic activity over 10/50HPF, high cellularity and obvious pleomorphism were all in the malignant group. In this group, tumor necrosis, adhesion in operation, tumor, over 5 cm in diameter, mitotic activity over 5/50HPF had significant differences among three groups and the 3 years survival rate had a significant difference in tumors with or without coagulative necrosis and also in tumors with or without mitotic activity over 5/50HPF.

CONCLUSIONSGISTs predominantly occurred in middle aged or old patients, the tumors had varied cell types and different arrangements, the immunohistochemical characters were positive for CD117 and CD34, negative for desmin, occasional positive for alpha-SMA, MSA, S-100 and PGP9.5, which were helpful to differentiate GIST from leiomyomas and Schwannomas. Coagulative necrosis, mitotic activity over 10/50HPF, high cellularity with obvious pleomorphism were also helpful parameters for diagnosis of malignancy aside from metastasis and invasion. Adhesion, over 5 cm in diameter and mitotic activity over 5/50HPF but less than 10/50HPF might be the potential malignant parameters.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Colonic Neoplasms ; metabolism ; pathology ; Female ; Gastrointestinal Neoplasms ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Intestinal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Rectal Neoplasms ; metabolism ; pathology ; Statistics as Topic ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo study the genetic basis of aberrant crypt foci (ACF), which serve as a very early morphological alteration during the development of carcinogenesis by analyzing the loss of heterozygosity (LOH).

METHODSDNA from 35 colorectal carcinomas (CRC) and 34 matched ACF were isolated by microdissection. LOH of microsatellite loci at 18q12, 18q21, 5q12, 5q21, 3p21, 2p16, 17q21, 17q11 and 11p13 was detected by means of ABI-SEQUENCER and GeneScan software was applied for analysis.

RESULTSThe rate of LOH in ACF (41.18%) was less than that in carcinoma (68.57%) (P < 0.05). The profile of LOH rates at loci 18q12, 5q12, 3p21, 17q21, 17q11, 11p13 and 2p16 in ACF was similar to that in carcinoma. The LOH frequencies on 18q12, 18q21, 5q12, 5q21, and 3p21 were higher than that on 17q11 and 11p13. However the rate at 18q21 and 5q21 in ACF was much lower than that in the carcinoma (P < 0.05). The co-existing carcinomas displayed more polypoid growth pattern and located more at the sigmoid colon and rectum. LOH in carcinomas did not correlate with the location, size, type of the carcinoma and Duke's stage.

CONCLUSIONSACF are putative preneoplastic lesions that might represent the earliest morphological lesion with the alteration at molecular genetic level. Our study provides further genetic evidence in the pathogenesis of colorectal carcinomas.

Chromosomes ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 18 ; Chromosomes, Human, Pair 2 ; Chromosomes, Human, Pair 3 ; Chromosomes, Human, Pair 5 ; Colorectal Neoplasms ; genetics ; pathology ; Humans ; Loss of Heterozygosity ; Precancerous Conditions

OBJECTIVETo analyze the DNA sequence characteristics of translocation t (X; 18) genomic breakpoints and to study the mechanism underlying chromosomal translocation t (X; 18) in synovial sarcoma.

METHODSTwo cases of synovial sarcoma were studied utilizing long-distance polymerase chain reaction (PCR) and sequence analysis to amplify the genomic DNA of translocation t (X; 18) breakpoints.

RESULTSTranslocation t (X; 18) was detected in both cases, which generated SYT-SSX1 and SYT-SSX2 fusion gene respectively. Sequence analysis revealed that intron 10 of SYT was fused to the intron 4 of SSX1 or SSX2. Sequences highly homologous to consensus recognition motifs of translin were found adjacent to breakpoints in all three genes. Breakpoints in the three genes were close to or even at several palindromic oligomer sequences. The breaks in intron 4 of SSX1 and SSX2 were near an Alu sequence. No Alu or other repetitive sequences were found 500 bp upstream or downstream from the break in intron 10 of SYT. One topoisomerase II consensus site was found between the two breakpoints but with considerable distance from intron 10 of SYT.

CONCLUSIONSAll three genes involved in synovial sarcomas contain characteristic sequence motifs in the breakpoint regions which may play an important role in the genesis of chromosomal translocation in synovial sarcoma.

Base Sequence ; Chromosomes, Human, Pair 18 ; Chromosomes, Human, X ; Cloning, Molecular ; DNA, Neoplasm ; analysis ; Humans ; Molecular Sequence Data ; Oncogene Proteins, Fusion ; genetics ; isolation & purification ; Sarcoma, Synovial ; genetics ; Sequence Analysis, DNA ; Translocation, Genetic

OBJECTIVETo explore the clinicopathological, immunohistochemical, and molecular biologic characteristics of esophageal stromal tumors and smooth muscle tumors.

METHODSTwenty four cases of esophageal mesenchymal tumors were reclassified by a panel of antibodies such as CD117, CD34 etc. The sequence of 11 exon of c-kit gene were detected in some cases.

RESULTSThere were 3 cases of esophageal stromal tumors, 20 leiomyomas, and 1 leiomyosarcoma. The 3 esophageal stromal tumors occurred in 3 men aged 71, 56 and 60 years respectively. The tumors originated from muscularis propria with the size of 4 cm, 8 cm and 14 cm in diameter. Microscopically, the tumor cells were spindle and epithelioid shaped with slightly basophilic appearance, arranged in intersecting fascicles, diffusing and palisading patterns. Immunohistochemically, the tumors were positive for CD117 and CD34. The mutation of 11 exon of c-kit gene was detected in one case. In comparison, esophageal leiomyomas occurred in a younger population. The age ranged from 30 to 60 years (mean age 41.6 years), 12 male cases, 8 female cases. 15 cases of esophageal leiomyomas were intramural tumors with a diameter of 0.8 - 10.5 cm (mean 4.5 cm) originating from muscularis propria and 5 cases which were intraluminal polyps with a diameter of 0.2 - 1.0 cm originating from muscularis mucosae. Leiomyomas were strongly eosinophilic in appearance, diffuse positivity for alpha-SMA, MSA, and desmin, and no c-kit gene mutation. One male case of leiomyosarcoma had a diameter of 5 cm and originated from muscularis mucosae and displayed a sausage-shaped polyp.

CONCLUSIONSLeiomyoma is still the most common mesenchymal tumor of the esophagus, the stromal tumor can be similar to gastrointestinal stromal tumors. Typical esophageal leiomyosarcoma is very rare and has different clinicopathologic and molecular biologic features.

Actins ; analysis ; Adult ; Aged ; Antigens, CD34 ; analysis ; Base Sequence ; Desmin ; analysis ; Esophageal Neoplasms ; genetics ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Leiomyoma ; genetics ; metabolism ; pathology ; Leiomyosarcoma ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Muscle, Smooth ; metabolism ; pathology ; Mutation ; Proto-Oncogene Proteins c-kit ; analysis ; genetics ; Stromal Cells ; metabolism ; pathology

Purpose: To detect the mRNA expression of epithelial skeleton protein CK19 in the peripheral blood of patients with colorectal cancer; to study its relationship to other clinicopathological parameters; and to discuss if the detection can help post-operative adjuvant therapy. Methods: A total of 39 blood samples from colorectal cancer patients were included in the study. Specific RT-PCR primers were used to avoid the amplification of pseudogenes. Results: Of 39 patients 31 showed CK19 mRNA expression (79.5%) . The patients in Dukes stage C and D showed higher frequency of CK19 mRNA expression than that in Dukes A and B (P

WTBZ]Breast cancer resistance protein (BCRP) is a recently discovered half-transporter belonging to the ABC transporter superfamily as P-glycoprotein(P-gp) and multiple resistance protein (MRP). The latest research results concerned BCRP on construction features of gene, relationship to differentiation of hemopoietic stem cell and correlated transport substrates were reviewed in the article and it's clinical significance was mentioned at the same time.

Objective To study the clinicopathological characteristics of hereditary nonpolyposis colorectal cancer (HNPCC) in Chinese population with different criteria and guidelines. Methods Twenty four families fulfilling Amsterdam Criteria (AC), 15 additional families fulfilling Japanese Criteria (JC) and the remaining 19 patients fitting Bethesda Guidelines (BG) were analyzed. Results In the 24 AC families there were 116 malignant tumor patients including 90 colorectal cancer (CRC) subjects and in the 15 JC families there were 54 malignant tumor patients including 33 CRC cases. The two groups displayed similar clinical features. Mean age of first CRC at diagnosis was 46.1 and 51.4 years old, respectively. The proximal colonic cancers accounted for 55.4% versus 44.8%. Synchronous and metachronous multiple CRCs occurred in 25.6% and 18.2% of patients respectively. Totally there were 55 extracolonic tumors in the two groups. Gastric and endometrial carcinomas were two most common extracolonic tumor types in our series. The tumors of the 34 probands showed more frequent exophytic growth pattern, higher occurance of poorly differentiated carcinoma, A / B Dukes stage and more Crohn's like lymphoid reaction ( P

Objective　To analyze the mutations of K-ras and APC gene in normal colorectal mucosa, aberrant crypt foci (ACF), adenoma and colorectal carcinoma(CRC); To study the genetic alteration in ACF and its possibility of being a molecular marker of very early colon cancer and to explore the relationship of ACF and colorectal adenoma. Methods　DNA from 35 CRC, 15 adenomas, 34 ACF and 15 cases of normal mucosa with mucous glands were isolated by micro-dissection. Direct gene sequencing of k-ras gene including codon 12, 13 and 61 as well as the mutation cluster region (MCR) of APC gene. Results　Mutation frequency of k-ras gene in ACF, adenoma and carcinoma was 17.6%(6/34), 13.3%(2/15), and 14.3%(5/35) respectively, showing no difference between the three pathologic changes. The ras gene mutation sites in adenomas, carcinomas and 4 ACF were limited to codon 12 (GGT→GAT), but in 2 ACF, they were located in codon 13 (GGC→GAC). K-ras gene mutation in ACF was found more frequently in old patients and in patients with polypoid cancers. No mutations were found in codon 61 in three types of tissue. Mutation rate of APC genes in adenomas and carcinomas was 22.9% (8/35) and 26.7%(4/15) respectively, which was higher than that of ACF 2.9%,(P<0.05). APC gene mutation in carcinomas was not correlated with age, location, size and differentiation. Conclusion　The morphological changes and gene mutation status are different in ACF and adenomas. ACF is a very early morphological lesion in the carcinogenesis of colorectal carcinoma. Therefore, ACF is considered to be the putative “microadenoma” where the development of colorectal carcinomas may be from “normal epithelium to ACF and then to carcinomas”.