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Immunohistochemical and genetic analysis of non-small cell and small cell gallbladder carcinoma and their precursor lesions.
Mod Pathol 2003; 16(4):299-308MP

Abstract

Gallbladder carcinomas can be highly lethal neoplasms. Relatively little is known about the genetic abnormalities that underlie these tumors, particularly with respect to their timing in neoplastic progression. The authors evaluated 5 noninvasive dysplasias and 33 invasive gallbladder carcinomas (6 small cell carcinomas, 27 non-small cell carcinomas, of which 16 were accompanied by an in situ carcinoma component) for expression of the protein products of the p16, p53, Dpc4, and pRB tumor suppressor genes by immunohistochemistry. Neoplasms were also evaluated for the presence of activating K-ras oncogene mutations. Seventy-five percent of non-small cell gallbladder carcinomas demonstrated loss of p16 expression, whereas 63% accumulated high levels of p53. Loss of Dpc4 and pRB expression was less frequent, seen in 19% and 4% of the neoplasms, respectively. Thirty percent of neoplasms harbored activating K-ras mutations. In contrast, 100% of the small cell carcinomas of the gallbladder demonstrated inactivation of the pRB/p16 pathway; 67% showed loss of pRB expression, and the other 33% lost p16 expression. Eighty-three percent of small cell carcinomas accumulated high levels of p53, whereas loss of Dpc4 expression and activating K-ras mutations were not found. Among 15 evaluable in situ components, 13 harbored the same alterations found in the invasive component. Inactivation of p16 and p53 occur in the majority of non-small cell gallbladder carcinomas. Dpc4 inactivation and K-ras mutations occur in a significant minority of cases. pRB loss is uncommon in non-small cell gallbladder carcinoma, but virtually all small cell carcinomas inactivate the p16/pRB pathway, usually by retinoblastoma protein loss. It is noteworthy that all of these alterations occur at the level of carcinoma in situ.

Authors+Show Affiliations

Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland 21231-2410, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12692194

Citation

Parwani, Anil V., et al. "Immunohistochemical and Genetic Analysis of Non-small Cell and Small Cell Gallbladder Carcinoma and Their Precursor Lesions." Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, vol. 16, no. 4, 2003, pp. 299-308.
Parwani AV, Geradts J, Caspers E, et al. Immunohistochemical and genetic analysis of non-small cell and small cell gallbladder carcinoma and their precursor lesions. Mod Pathol. 2003;16(4):299-308.
Parwani, A. V., Geradts, J., Caspers, E., Offerhaus, G. J., Yeo, C. J., Cameron, J. L., ... Argani, P. (2003). Immunohistochemical and genetic analysis of non-small cell and small cell gallbladder carcinoma and their precursor lesions. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 16(4), pp. 299-308.
Parwani AV, et al. Immunohistochemical and Genetic Analysis of Non-small Cell and Small Cell Gallbladder Carcinoma and Their Precursor Lesions. Mod Pathol. 2003;16(4):299-308. PubMed PMID: 12692194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunohistochemical and genetic analysis of non-small cell and small cell gallbladder carcinoma and their precursor lesions. AU - Parwani,Anil V, AU - Geradts,Joseph, AU - Caspers,Eric, AU - Offerhaus,G Johan, AU - Yeo,Charles J, AU - Cameron,John L, AU - Klimstra,David S, AU - Maitra,Anirban, AU - Hruban,Ralph H, AU - Argani,Pedram, PY - 2003/4/15/pubmed PY - 2003/11/7/medline PY - 2003/4/15/entrez SP - 299 EP - 308 JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JO - Mod. Pathol. VL - 16 IS - 4 N2 - Gallbladder carcinomas can be highly lethal neoplasms. Relatively little is known about the genetic abnormalities that underlie these tumors, particularly with respect to their timing in neoplastic progression. The authors evaluated 5 noninvasive dysplasias and 33 invasive gallbladder carcinomas (6 small cell carcinomas, 27 non-small cell carcinomas, of which 16 were accompanied by an in situ carcinoma component) for expression of the protein products of the p16, p53, Dpc4, and pRB tumor suppressor genes by immunohistochemistry. Neoplasms were also evaluated for the presence of activating K-ras oncogene mutations. Seventy-five percent of non-small cell gallbladder carcinomas demonstrated loss of p16 expression, whereas 63% accumulated high levels of p53. Loss of Dpc4 and pRB expression was less frequent, seen in 19% and 4% of the neoplasms, respectively. Thirty percent of neoplasms harbored activating K-ras mutations. In contrast, 100% of the small cell carcinomas of the gallbladder demonstrated inactivation of the pRB/p16 pathway; 67% showed loss of pRB expression, and the other 33% lost p16 expression. Eighty-three percent of small cell carcinomas accumulated high levels of p53, whereas loss of Dpc4 expression and activating K-ras mutations were not found. Among 15 evaluable in situ components, 13 harbored the same alterations found in the invasive component. Inactivation of p16 and p53 occur in the majority of non-small cell gallbladder carcinomas. Dpc4 inactivation and K-ras mutations occur in a significant minority of cases. pRB loss is uncommon in non-small cell gallbladder carcinoma, but virtually all small cell carcinomas inactivate the p16/pRB pathway, usually by retinoblastoma protein loss. It is noteworthy that all of these alterations occur at the level of carcinoma in situ. SN - 0893-3952 UR - https://www.unboundmedicine.com/medline/citation/12692194/Immunohistochemical_and_genetic_analysis_of_non_small_cell_and_small_cell_gallbladder_carcinoma_and_their_precursor_lesions_ L2 - http://dx.doi.org/10.1097/01.MP.0000062656.60581.AA DB - PRIME DP - Unbound Medicine ER -