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Biomedical subjects

J Rüschoff

Publications and source records attributed to J Rüschoff.

At least 37 records · Page 2Linked to original sources
PubMed2000

Sequence analysis of the mismatch repair gene hMSH6 in the germline of patients with familial and sporadic colorectal cancer.

To evaluate the involvement of hMSH6 in colorectal cancer, the complete coding sequence and flanking intron regions of the gene were analyzed by DNA sequencing in 10 patients fulfilling Bethesda Guidelines for colorectal tumors and 10 patients with sporadic colorectal carcinoma. In addition, 10 mono- and 10 dinucleotide repeat markers were analyzed for microsatellite instability. A protein-truncating T insertion at codon 218 was identified in the index person of a hereditary non-polyposis colorectal cancer (HNPCC)-like kindred and was accompanied by a somatic T deletion in the tumor. The tumor of this patient was positive for mono- but negative for dinucleotide repeat instability and lacked allelic losses at loci frequently affected in colorectal carcinomas. A novel amino acid change, F340S, was found in a patient with sporadic colon and breast cancer and leukemia but was not detected in 246 chromosomes from healthy anonymous blood donors. In addition, we describe 2 silent and 15 intronic sequence variants not previously reported. Although the frequency is low, we present further evidence for hMSH6 germline mutations that predispose patients to HNPCC-like phenotypes and suggest that mono- and dinucleotide repeat instability testing may be useful for distinguishing between individuals harboring an hMSH2 or hMLH1 mutation and a mutation of the hMSH6 gene.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Prognostic value of microscopic peritoneal dissemination: comparison between colon and gastric cancer.

PURPOSE: We evaluated the incidence and prognostic relevance of microscopic intraperitoneal tumor cell dissemination of colon cancer in comparison with dissemination of gastric cancer as a rational for additive intraperitoneal therapy. METHODS: Peritoneal washouts of 90 patients with colon and 111 patients with gastric cancer were investigated prospectively. Sixty patients with benign diseases and 8 patients with histologically proven gross visible peritoneal carcinomatosis served as controls. Intraoperatively, 100 ml of warm NaCl 0.9 percent were instilled and 20 ml were reaspirated. In all patients hematoxylin and eosin staining (conventional cytology) was performed. Additionally, in 36 patients with colon cancer and 47 patients with gastric cancer, immunostaining with the HEA-125 antibody (immunocytology) was prepared. The results of cytology were assessed for an association with TNM category and cancer grade, based on all patients, and with patient survival, among the R0 resected patients. RESULTS: In conventional cytology 35.5 percent (32/90) of patients with colon cancer and 42.3 percent (47/111) of patients with gastric cancer had a positive cytology. In immunocytology 47.2 percent (17/36) of patients with colon cancer and 46.8 percent (22/47) of patients with gastric cancer were positive. In colon cancer, positive conventional cytology was associated with pT and M category (P = 0.044 and P = 0.0002), whereas immunocytology was only associated with M category (P = 0.007). No association was found between nodal status and immunocytology in colon cancer and with the grading. There was a statistically significant correlation between pT M category and conventional and immunocytology in gastric cancer (P < 0.0015/P = 0.007 and P < 0.001/P = 0.009, respectively). Positive immunocytology was additionally associated with pN category (P = 0.05). In a univariate analysis of R0 resected patients (no residual tumor), positive immunocytology was significantly related to an unfavorable prognosis in patients with gastric cancer only (n = 30). Mean survival time was significantly increased in patients with gastric cancer with negative cytology compared with positive cytology (1,205 (standard error of the mean, 91) vs. 771 (standard error of the mean, 147) days; P = 0.007) but not in patients with colon cancer (1,215 (standard error of the mean, 95) vs. 1,346 (standard error of the mean, 106) days; P = 0.55). CONCLUSIONS: Because microscopic peritoneal dissemination influences survival time after R0 resections only in patients with gastric but not with colon cancer, our results may provide a basis for a decision on additive, prophylactic (intraperitoneal) therapy in gastric but not colon cancer.

Analysis of Variance↗
PubMed2000

Molecular analysis of microdissected tumors and preneoplastic intraductal lesions in pancreatic carcinoma.

Little or no data exist concerning the inactivation of tumor suppressor genes in intraductal lesions surrounding invasive ductal pancreatic carcinomas. Using a novel improved primer extension and preamplification polymerase chain reaction, we analyzed microdissected paraffin-embedded specimens of pancreatic carcinoma (n = 29) and their corresponding pancreatic intraductal lesions (PIL, n = 331) for loss of heterozygosity (LOH) of p16(INK4), DPC4, and p53 by microsatellite analysis and for p53 protein by immunohistochemistry. LOH at the p16(INK4) locus (9p21) was found in nine of 22 informative tumors (41%), in 15 of 25 tumors (60%) at the DPC4 locus (18q21.1), and in 22 of 27 tumors (81%) at the p53 locus (17p13). Homozygous deletions of p16(INK4) and DPC4 were found in eight of 22 (36%) and four of 25 tumors (16%), respectively. Furthermore, 24 of 29 tumors (83%) revealed considerable intratumoral genetic heterogeneity. In 165 of 277 PILs (60%) having suitable DNA for microsatellite analysis, alterations in at least one tumor suppressor gene were found. In individual PILs, up to three alterations were detected, and p53 LOH occurred even in morphologically normal-appearing ductal epithelium near the tumor. Although deletions of all three tumor suppressor genes were found in PILs without nuclear atypia, there was a tendency toward earlier LOH of p16(INK4) compared to DPC4 and p53 in these lesions. LOH in tumors accompanied positive p53 immunohistochemistry in 81% but only in 38% in PILs.

Carcinoma, Intraductal, Noninfiltrating↗
PubMed2000

Microsatellite analysis in rheumatoid arthritis synovial fibroblasts.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic disease characterised by irreversible destruction of the affected joints. As aggressive transformed-appearing synovial fibroblasts are commonly found at the site of invasion of the rheumatoid synovium into the adjacent cartilage and bone, the presence of microsatellite instability (MSI) and expression of mismatch repair enzymes as a possible mechanism in the alteration of these cells was examined. METHODS: DNA was extracted from the synovial fibroblasts and blood of 20 patients with long term RA undergoing joint replacement, and the presence of MSI was studied at 10 microsatellite loci. In addition, immunohistochemistry was performed to evaluate the expression of the two major mismatch repair enzymes (hMLH1 and hMSH2) in rheumatoid synovium. RESULTS: MSI could not be detected in any of the fibroblast cell populations derived from the 20 different rheumatoid synovial samples. In addition, strong expression of mismatch repair enzymes could be seen in numerous cells, including fibroblasts, throughout the synovium. CONCLUSIONS: Applying the currently used and established markers for MSI, the data show for the first time that MSI does not appear to have an important role in alteration of rheumatoid synovial fibroblasts into an aggressive phenotype. On the other hand, strong mismatch repair enzyme synthesis in rheumatoid synovium supports the hypothesis of continuing DNA repair, presumably due to long term, inflammation induced DNA damage.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Microsatellite instability in tumor and nonneoplastic colorectal cells from hereditary non-polyposis colorectal cancer and sporadic high microsatellite-instable tumor patients.

Genetic alterations such as loss of heterozygosity (LOH) and microsatellite instability (MSI) have been frequently studied in various tumor types. Genetic heterogeneity of nonneoplastic cells has not yet been sufficiently investigated. However, genomic instability in normal cells could be a potentially important issue, in particular when these cells are used as reference in LOH and MSI analyses of tumor samples. In order to investigate possible genetic abnormalities in normal colorectal cells of tumor patients, MSI analyses of normal colonic mucosa were performed. Up to 15 different laser-microdissected normal regions containing 50-150 cells were investigated in each of 15 individual microsatellite-stable, sporadic high microsatellite-instable (MSI-H) and hereditary non-polyposis coli cancer (HNPCC) colorectal cancer patients. Frequent MSI and heterogeneity in the MSI pattern were found both in normal and tumor cells from 10 HNPCC and sporadic MSI-H tumor patients whose tumors had defect mismatch repair protein expressions. This observation shows that MSI can also occur in nonneoplastic cells which has to be considered in MSI analyses for molecular HNPCC screening. In addition, considerable genetic heterogeneity was detected in all MSI-H (sporadic and HNPCC) tumors when analyzing five different regions with less than 150 cells, respectively. These differences were not detectable in larger tumor regions containing about 10,000 cells. Thus, heterogeneity of the MSI pattern (e.g. intratumoral MSI) is an important feature of tumors with the MSI-H phenotype.

Cell Separation↗
PubMed2000

[beta-Catenine as a genomic target of high-grade microsatellite instability in colorectal cancer].

AIMS: Various inherited and acquired alterations affecting the genes and gene products of the WNT pathway appear to be involved in the different molecular routes leading to colorectal cancer (CRC). This study was initiated to investigate the prevalence of somatic mutations in the beta-catenin gene (CTNNB1) and the associated pathology in CRC with defective DNA mismatch repair. METHODS: Paraffin and/or frozen sections of 33 primary CRC (including any liver and lymph node metastases present) with high-grade microsatellite instability (MSI-H; i.e. with > or = 5 unstable microsatellite markers of 10 tested) were polytopically fractionated by microdissection. Genomic and c-DNA samples were sequenced across exons 2-4 of CTNNB1 and the expression patterns of beta-catenin (beta-C) analyzed by immunohistology and Western blotting. RESULTS: Seven somatic mutations affecting phosphorylation sites of exon 3 (2 deletions also encompassing parts of either intron 2 or exon 4 [delta X2/3 bzw. delta X3/4] and 5 missense mutations [2 x T41A, 2 x S45F, S45P]) were identified. Two mutations (delta X3/4 and S45F) were concordantly present in CRC primaries and their respective metastases whereas the S45P mutation was restricted to a hepatic metastasis. In the delta X2/3 CRC primary only a shortened 66 kD CTNNB1 gene product was present while its associated liver metastasis showed a total loss of beta-C expression. CONCLUSIONS: Both exon 3 and the entire locus coding for beta-C are somatically altered in approximately 20% of CRC with MSI-H at different stages of tumor progression. Thus CTNNB1 appears to be a genomic target for complex oncogenic mutations and deletional processes in a substantial fraction of this molecular subset of CRC.

Cadherins↗
PubMed1999

Molecular diagnostics of cancer predisposition: hereditary non-polyposis colorectal carcinoma and mismatch repair defects.

Hereditary non-polyposis colorectal carcinoma accounts for 5-13% of all colorectal carcinomas and is inherited in a dominant fashion. Two different forms can be distinguished. Type I is restricted to colorectal cancers, whereas type II patients acquire acolorectal, endometrial, gastric, small intestinal and transitional carcinomas of the upper urinary tract. Germline mutations in the human mismatch repair genes (hMSH2, hMSH6, hMLH1, hPMS2) account for the majority of hereditary non-polyposis colorectal carcinoma. As a result of the mismatch repair deficiency, replication errors are not repaired, resulting in a mutator phenotype. Simple repetitive sequences (microsatellites) are especially prone to replication errors and analysis of their stability combined with immunohistochemical analysis of mismatch repair protein expression provides a rapid diagnostic strategy. For patients either (1) fulfilling the Amsterdam criteria for HNPCC, (2) with synchronous or metachronous hereditary non-polyposis colorectal carcinoma-related tumors, (3) with hereditary non-polyposis colorectal carcinoma-related tumors before the age of 45 and/or (4) with right sided CRC and mucinous, solid, or cribriform growth patterns, screening for mismatch repair deficiencies should be performed. The identification of colorectal cancers displaying a mutator phenotype has implications for both treatment and prognosis.

Adaptor Proteins, Signal Transducing↗
PubMed1999

[Restrictive dermopathy].

Restrictive dermopathy is a rare, fatal, autosomal recessive, congenital skin disease. Rigidity of translucent thin skin, which is thus highly vulnerable and tears, spontaneously causes intra-uterine fetal akinesia or hypokinesia deformation sequence (FADS), characteristic dysmorphic facies with fixed open mouth in O position, and generalized joint contractures (arthrogryposis). Polyhydramnios and pulmonary hypoplasia are distinctive manifestations, leading to respiratory insufficiency and premature delivery at about 31 weeks of gestation. We report on a case of a prematurely born infant who presented with the typical morphological features and describe the light- and electron-microscopical findings as described in the literature.

Abnormalities, Multiple↗
PubMed1999

Assessment of microsatellite instability and loss of heterozygosity in sporadic keratoacanthomas.

Variations in the length of simple repetitive tandem repeats (microsatellite instability, MIN) between constitutive and tumour DNA, which is characteristic of tumours in patients affected with hereditary nonpolyposis colon cancer (HNPCC), have been found to be very important in the carcinogenesis of a variety of human neoplasms. Recently, MIN has been found in sebaceous and colorectal tumours as well as in keratoacanthomas of Muir-Torre syndrome. In order to elucidate the significance of both MIN and loss of heterozygosity (LOH) in the pathogenesis of sporadic keratoacanthomas, the presence of MIN and LOH at five loci [chromosome 5q21 (D5S346, APC), 9p21 (D9S171, p16), 10pter (D10S89, Mfd28), 11p (D11S904) and 17p12 (D17S520, p53)] was evaluated. MIN was found at only one locus (p53) in 1 of 12 keratoacanthomas and no evidence for the presence of LOH could be detected. Our results suggest that, in contrast to keratoacanthomas associated with Muir-Torre syndrome, neither MIN nor LOH appear to be significant in the induction of sporadic keratoacanthomas.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed1999

Expression of wild-type ret, ret/PTC and ret/PTC variants in papillary thyroid carcinoma in Germany.

INTRODUCTION: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Although the clinical course is usually rather benign, a subset of tumors is more aggressive. The ret/PTC oncogene was found only in PTC, with varying frequencies of up to 30%. Recently, two new variants of ret/PTC could be identified in post-Chernobyl PTCs, which raised the possibility that the prevalence of ret/PTC in non-radiation-induced PTCs might be higher than previously described. Normal thyroid cells do not express wild-type ret, but there is evidence that ret activation from any cause, including wild-type ret, occurs in more than a half of papillary tumors. METHODS: We used reverse transcription polymerase chain reaction and sequencing to examine wild-type ret and all five forms of ret/PTC known today in 99 PTCs from Hannover, Dusseldorf, Halle and Regensburg. Our method could also detect other variants within the known breakpoint regions. The presence of the ret tyrosine-kinase domain was examined by immunohistochemistry. RESULTS: Seven PTC1-positive tumors and one PTC3-positive tumor (8%), but none with the new variants or other variants of PTC1, 2 or 3 could be detected. Of 43 tumors examined, 20 showed expression of wild-type ret mRNA and staining of ret protein located predominantly to the cell membrane. CONCLUSION: Variants of ret/PTC do not substantially contribute to non-radiation-related ret/PTC-positive tumors, and the prevalence of ret/PTC in Germany is low in contrast to the high rate of wild-type ret expression. Thus, expression of wild-type ret should be examined for pathogenic, prognostic and possible therapeutic implications.

Carcinoma, Papillary↗
PubMed1999

Multiple mutation analyses in single tumor cells with improved whole genome amplification.

Combining whole genome amplification (WGA) methods with novel laser-based microdissection techniques has made it possible to exploit recent progress in molecular knowledge of cancer development and progression. However, WGA of one or a few cells has not yet been optimized and systematically evaluated for samples routinely processed in tumor pathology. We therefore studied the value of established WGA protocols in comparison to an improved PEP (I-PEP) PCR method in defined numbers of flow-sorted and microdissected tumor cells obtained both from frozen as well as formalin-fixed and paraffin-embedded tissue sections. In addition, the feasibility of I-PEP-PCR for mutation analysis was tested using clusters of 50-100 unfixed tumor cells obtained by touch preparation of ten breast carcinomas by conventional sequencing of exon 7 and 8 of the p53 gene. Finally, immunocytochemically stained microdissected single disseminated tumor cells from bone marrow aspirates were investigated with respect to mutations in codon 12 of Ki-ras by restriction fragment length polymorphism (RFLP)-PCR after I-PEP-PCR. The modified I-PEP-PCR protocol was superior to the original PEP-PCR and DOP-PCR protocols concerning amplification of DNA from one cell (efficiency rate I-PEP-PCR 40% versus PEP-PCR 15% and DOP-PCR 30%) and five cells (efficiency rate I-PEP-PCR 100% versus PEP-PCR 33% and DOP-PCR 20%). Preamplification by I-PEP allowed 100% sequence accuracy in > 4000 sequenced base pairs and Ki-ras mutation detection in isolated single disseminated tumor cells. For reliable microsatellite analysis of I-PEP-preamplified DNA, at least 10 unfixed cells from fluorescence-activated cell sorting, 10 cells from frozen tissue, or at least 30 cells from formalin-fixed and paraffin-embedded tissue sections were required. Thus, I-PEP-PCR allowed multiple reliable microsatellite analyses suited for microsatellite instability and losses of heterozygosity and mutation analysis even at the single cell level, rendering this technique a powerful new tool for molecular analyses in diagnostic and experimental tumor pathology.

Bone Marrow Neoplasms↗
PubMed1999

Immunocytology improves prognostic impact of peritoneal tumour cell detection compared to conventional cytology in gastric cancer.

AIMS: Studies on the value of peritoneal tumour cell dissemination for prognosis in gastric cancer using various methods to detect tumour cells have produced conflicting conclusions. We studied the incidence and prognostic relevance of microscopic intraperitoneal tumour cell dissemination in gastric cancer, comparing conventional and immunocytological detection. METHODS: Peritoneal wash-outs of 111 consecutive gastric patients without overt peritoneal carcinomatosis, including 75 curatively resected patients, were studied. Sixty patients with benign disorders served as controls. 100 ml of warm NaCl 0.9% was instilled intraoperatively and 20 ml was reaspirated. The specimens were stained peri-operatively with H&E. In the last 47 patients (30 of whom were curatively resected) additional immunostaining with the HEA-125 antibody was performed. The results of cytology were correlated with the TNM categories and with post-operative follow-up. RESULTS: Of the patients, 42.3% and 48.9% were positive when conventional and immunocytological staining were employed, respectively. Conventional cytology was significantly associated with the pT and M categories. Immunocytology was significantly associated with the pT, pN and M caterogies. In four of 30 curatively resected patients (13.3%), the results of conventional and immunocytology were different. Three patients with positive immunocytology but negative conventional cytology died during follow-up (median follow-up 45.3 months), whereas one patient with positive conventional but negative immunocytology is still alive. In an univariate analysis 4 years post-surgery, positive immunocytology was significantly associated with an unfavourable prognosis in patients with curatively resected gastric cancer. While only 28.6% (six of 21) of the patients with negative immunocytology had died, this proportion increased to 77.8% (seven of nine) with positive immunocytology (P=0.018). The mean survival of negative vs positive patients amounted to 1205+/-91 vs 772+/-147 days (P=0.007). In contrast, in conventional cytology we found no significantly different survival time between negative and positive patients. CONCLUSIONS: Immunocytology seems to be superior to conventional cytology and should be preferred.

Case-Control Studies↗
PubMed1999

[Correlation between histological and molecular mechanisms of carcinogenesis in stomach cancer].

Since gastric cancer is an exceptional heterogeneous tumor conflicting results have been obtained about the relationship between genotype and phenotype. From the molecular point of view gastric carcinoma diffuse type forms a distinct entity which is microsatellite stable, has almost no p53 mutations and exhibits in at least half of the cases mutations in the E-cadherin gene. In contrast, all other gastric carcinomas comprise a heterogeneous group of which about one third exhibits microsatellite instability (MSI) but no p53 protein stabilization or gene mutations. These tumors are either of pure intestinal (glandular) type or show large solid (medullary) tumor cell clusters. Thereby, in sporadic gastric cancer MSI is caused by loss of hMLH1 expression due to hypermethylation of the promotor region rather than by mutation of the gene itself. Tumors that are microsatellite stable (MSS) and show p53 alterations are either intestinal (about 70%) or a mixed-type encompassing at least 5% glandular and poorly differentiated diffuse components (about 30%). Whereas pure diffuse type gastric cancer is unlikely to develop from intestinal type carcinoma, this may, however, be the case in some advanced mixed-type gastric cancers.

Base Pair Mismatch↗
PubMed1999

[Aspirin suppresses microsatellite instability].

Nonsteroidal anti-inflammatory drugs (NSAIDs) exhibit cancer preventive effects and have been shown to induce regression of adenomas in FAP patients. In order to elucidate the probable underlying mechanism, the effect of NSAIDs on mismatch repair related microsatellite instability was investigated. Six colorectal cancer cell lines all but one deficient for human mismatch repair (MMR) genes were examined for microsatellite instability (MSI) prior and after treatment with Aspirin or Sulindac. For rapid in vitro analysis of MSI a microcloning assay was developed by combining Laser microdissection and random (PEP-) PCR prior to specific MSI-PCR. Effects of NSAIDs on cell cycle and apoptosis were systematically investigated by using flow cytometry and cell-sorting. MSI frequency in cells deficient of MMR genes (hMSH2, hMLH1, hMSH6) was markedly reduced after long-term (> 10 weeks) NSAID treatment. This effect was reversible, time- and concentration dependent. However, in the hPMS2 deficient endometrial cancer cell line (HEC-1-A) the MSI phenotype kept unchanged. According to cell sorting, non-apoptotic cells were stable and apoptotic cells were unstable. These results suggest that aspirin/sulindac induces a genetic selection for microsatellite stability in a subset of MMR-deficient cells and may thus provide an effective prophylactic therapy for HNPCC related colorectal carcinomas.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Aspirin suppresses the mutator phenotype associated with hereditary nonpolyposis colorectal cancer by genetic selection.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are well-known cancer preventives, which have been largely attributed to their antiproliferative and apoptosis-inducing activities. In this study, we show that microsatellite instability (MSI) in colorectal cancer cells deficient for a subset of the human mismatch repair (MMR) genes (hMLH1, hMSH2, and hMSH6), is markedly reduced during exposure to aspirin or sulindac [or Clinoril, which is chemically related to indomethacin (Indocin)]. This effect was reversible, time and concentration dependent, and appeared independent of proliferation rate and cyclooxygenase function. In contrast, the MSI phenotype of a hPMS2-deficient endometrial cancer cell line was unaffected by aspirin/sulindac. We show that the MSI reduction in the susceptible MMR-deficient cells was confined to nonapoptotic cells, whereas apoptotic cells remained unstable and were eliminated from the growing population. These results suggest that aspirin/sulindac induces a genetic selection for microsatellite stability in a subset of MMR-deficient cells and may provide an effective prophylactic therapy for hereditary nonpolyposis colorectal cancer kindreds where alteration of the hMSH2 and hMLH1 genes are associated with the majority of cancer susceptibility cases.

Adaptor Proteins, Signal Transducing↗
PubMed1998

[Molecular cancer disposition diagnosis exemplified by colorectal carcinoma. What is the contribution of pathology?].

During the last few years, the molecular basis of several cancer predisposition syndromes has been discovered which offers new tools for cancer prevention and early detection. This will be demonstrated in one of the most frequent hereditary cancer syndromes, namely the hereditary nonpolyposis colorectal cancer (HNPCC) which accounts for about 5% to 8% of CRC. Thereby, families with exclusively CRC (Lynch type I syndrome) and those with extracolonic cancers especially of endometrium, stomach, small bowel and upper urinary tract (Lynch type II syndrome) can be discriminated. At the molecular level, HNPCC is caused by germline mutations in one of the mismatch repair genes (hMSH2, hMLH1, hMSH6, hPMS2). Thus, nucleotide mispairings occurring particularly within simple repetitive genomic sequences (microsatellites) during replication are no longer be repaired properly and can be demonstrated by PCR as so-called microsatellite instability (MSI). Since more than 90% of HNPCC associated and only about 15% of sporadic CRC show MSI, this test is a useful tool for HNPCC screening. In case of a negative result HNPCC is highly unlikely. In positive cases (with > or = 2 out of 5 unstable defined microsatellite markers) the definite molecular diagnosis can only be obtained by sequencing the mismatch repair genes from the patient's blood or normal DNA. As immunohistochemistry reveals loss of hMSH2 or hMLH1 expression in most MSI positive CRC, these data provide useful information for the sequencing strategy. Molecular tumor screening by MSI test and immunohistochemistry is recommended in patients i.) with a positive family history (acc. to the Amsterdam criteria), ii.) suffering from multiple HNPCC related carcinomas, iii.) with HNPCC related cancer before 45 ys of age, and iv.) with right-sided CRC exhibiting medullary, signet-ring or mucinous differentiation. Finally, these tests as well as genetic counseling and treatment of the patient need to be done by an interdisciplinary approach. Thereby, the pathologist can substantially contribute to identify HNPCC related carcinomas either by clinical or morphological criteria and to initiate the molecular screening test.

Cell Transformation, Neoplastic↗