Allelic Loss of Chromosome 18q and Prognosis in Colorectal Cancer

Jen, Jin; Kim, Hoguen; Piantadosi, Steven; Liu, Zong Fan; Levitt, Roy C.; Sistonen, Pertti; Kinzler, Kenneth W.; Vogelstein, Bert; Hamilton, Stanley R.

doi:10.1056/nejm199407283310401

Cited by 644 publications

(387 citation statements)

References 47 publications

Supporting

Mentioning

349

Contrasting

Unclassified

Order By: Relevance

“…Recent molecular studies suggest that the process of tumorigenesis in colorectal cancer proceeds through a series of genetic alterations (Fearon and Vogelstein, 1990). Two reports have shown that allelic loss on chromosome 18q (DCC gene) is associated with poor prognosis in Dukes' stage B (O'Connel et al, 1992;Jen et al, 1994). Further studies are needed, however, to clarify how genetic alterations can contribute to prognosis.…”

Section: Discussionmentioning

confidence: 99%

Stromal tenascin distribution as a prognostic marker in colorectal cancer

Kressner

Lindmark²,

Tomasini-Johansson³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary A total of 169 colorectal adenocarcinomas, obtained from patients with a median follow-up of 6.5 years, were studied with immunohistochemical staining on cryosections using a monoclonal anti-tenascin antibody to evaluate the possible association between the staining patterns and tumour stage, tumour differentiation and survival. We found two different staining patterns in the tumour stroma -a diffuse stromal fibrillar staining in 92 out of 169 (54%) tumours and a subglandular staining in the remaining 77 tumours. When the entire group of patients (P < 0.01) and the group of potentially cured patients (P < 0.03) were analysed univariately, it was found that diffuse stromal fibrillar staining was associated with a shorter survival time than subglandular staining. In a multivariate analysis, the Dukes' stage and age were independent prognostic factors, whereas the tenascin expression did not retain a clear independent relationship to survival (P = 0.06).Hence, it appears that the tumour expression of tenascin may be a potential prognostic marker in colorectal cancer, in so far as a diffuse stromal fibrillar staining pattern seems to indicate an increased risk of poor outcome. However, after adjustment for age and Dukes' stage, the additional prognostic value of tenascin remains to be established in further analyses.Keywords: tenascin; colorectal cancer; tumour stage; tumour differentiation; survival; immunohistochemistry Tenascin is a large hexameric extracellular matrix protein that is present during embryonic development but essentially absent in normal adult tissues (Schenk and Chiquet-Ehrismann, 1994) and is expressed only at low levels or in a very restricted distribution. Several tenascin isoforms have been described . Tenascin has been suggested to be of importance in the normal healing process and in tumours, in which its role is presumed to be connected with cell adhesion and detachment, cell growth, cell migration and angiogenesis (Mackie et al, 1988;Ekblom and Aufterheide, 1989;Erickson and Bourdon, 1989; ChiquetEhrismann, 1993;Hahn et al, 1995; Joshi et al, 1995). It has been proposed that, although tenascin has no cell adhesion activity, it does affect the cell shape and, thus, may inhibit cell attachment to other extracellular proteins, including fibronectin (Mackie, 1994). It is also thought that tenascin plays a role in coordinating the provisional extracellular matrix surrounding the cancer tissue (Sakakura and Kusakabe, 1994).Several reports have shown an up-regulation of tenascin in various tumour stroma, such as breast (Moch et al, 1993;Shoji et al, 1993;Yoshida et al, 1995), lung (Natali and Zardi, 1989), prostatic (Ibrahim et al, 1993) and gastric carcinomas (Ikeda et al, 1995;Ilunga and Iriyama, 1995). Studies of this putative marker of the tumour matrix are also of considerable interest in colorectal cancer (Sugawara et al, 1991;Riedel et al, 1992;Sakai et al, 1993;Hauptmann et al, 1995;Riedel et al, 1995) because of the potential involvement of tenascin (or tenascin-like proteins) i...

show abstract

Section: Discussionmentioning

confidence: 99%

Stromal tenascin distribution as a prognostic marker in colorectal cancer

Kressner

Lindmark²,

Tomasini-Johansson³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…Amplicon detection used standard 7% polyacrylamide sequencing gel electrophoresis and autoradiography as previously described. 25 The size standard was generated using Phi-X 174 digested with HinfI (Gibco/BRL, Rockville, MD), ␣-32 P-dATP, and Klenow (Gibco/BRL) per manufacturer's instructions.…”

Section: Pcr and Microsatellite Analysismentioning

confidence: 99%

Detection of Microsatellite Instability by Fluorescence Multiplex Polymerase Chain Reaction

Berg

Glaser

Thompson

et al. 2000

The Journal of Molecular Diagnostics

Self Cite

139

121

View full text Add to dashboard Cite

We have created a clinical molecular diagnostic assay to test for microsatellite instability (MSI) at multiple loci simultaneously in paraffin-embedded surgical pathology colon resection specimens. This fluorescent multiplex polymerase chain reaction (PCR) assay analyzes the five primary microsatellite loci recommended at the 1997 National Cancer Institute-sponsored conference on MSI for the identification of MSI or replication errors in colorectal cancer: Bat-25, Bat-26, D2S123, D5S346, and D17S250. Amplicon detection is accomplished by capillary electrophoresis using the ABI 310 Genetic Analyzer. Assay validation compared 18 specimens previously assessed by radioactive PCR and polyacrylamide gel electrophoresis detection to results generated by the reported assay. Germline and tumor DNA samples were amplified in separate multiplex PCR reactions, sized in separate capillary electrophoresis runs, and compared directly to identify novel length alleles in tumor tissue. A concordance of 100% between the two modalities was achieved. The multiplex assay routinely detected a subpopulation of 10% tumor alleles in the presence of 90% normal alleles. A novel statistical model was generated that corroborates the validity of using results generated by analysis of five independent microsatellites to achieve a single overall MSI diagnosis. The assay presented is superior to standard radioactive monoplex PCR, polyacrylamide gel electrophoretic analysis, primarily due to the multiplex PCR format. (J Mol Diag 2000, 2:20 -28)Microsatellite instability (MSI), or replication error, is a manifestation of genomic instability arising in a variety of human neoplasms where tumor cells have a decreased overall ability to faithfully replicate DNA. This phenomenon has been shown to be a frequent, if not obligatory, surrogate marker of underlying functional inactivation of one of the human DNA mismatch repair (MMR) genes. [1][2][3][4][5][6]

show abstract

“…14 Allelic loss on chromosome 18q is found in approximately 70% of CRCs and has been associated with worse prognosis in stage II and III tumours. 15, 16 Jen et al found that stage II patients who retained both 18q alleles have an excellent 5-year survival of 93% compared to 54% of those who had lost one allele. 16 This data suggests that patients with stage II disease who have a deletion on chromosome 18q have a more aggressive clinical course and may represent a subset of stage II patients who would benefit from adjuvant chemotherapy.…”

Section: Colorectal Cancer Biologymentioning

confidence: 99%

“…15, 16 Jen et al found that stage II patients who retained both 18q alleles have an excellent 5-year survival of 93% compared to 54% of those who had lost one allele. 16 This data suggests that patients with stage II disease who have a deletion on chromosome 18q have a more aggressive clinical course and may represent a subset of stage II patients who would benefit from adjuvant chemotherapy. Furthermore, a recent study by Watanabe et al found that retention of both 18q alleles predicted for favourable outcome after adjuvant 5FU-based chemotherapy in stage III CRC.…”

Section: Colorectal Cancer Biologymentioning

confidence: 99%