Genetic Alterations in Goblet Cell Carcinoids of the Vermiform Appendix and Comparison with Gastrointestinal Carcinoid Tumors

Mirela Stancu, Tsung Teh Wu, Charita Wallace, Patrick S. Houlihan, Stanley R. Hamilton, Asif Rashid

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Goblet cell carcinoid is a relatively rare neuroendocrine tumor of the vermiform appendix with poorly understood molecular pathogenesis. We studied the clinicopathologic features and genetic alterations, including allelic loss of chromosomes 11q, 16q, and 18q; sequencing of the K-ras, β-catenin, and DPC4 (SMAD4) genes; and p53 overexpression and loss of DPC4 by immunohistochemistry; in 16 goblet cell carcinoids. We compared the allelic loss in goblet cell carcinoids to those in 18 gastrointestinal carcinoid tumors. For goblet cell carcinoids, appendiceal perforation was the most common (70%, 7/10) clinical presentation. The mean tumor size was 2.0 ± 1.5 cm (range, 0.4 to 4.5 cm). The tumor invaded to appendiceal serosa in 50% (8/16) of patients, and two patients had metastasis in lymph nodes or adjoining viscera. With mean follow-up of 24 ± 14 months (median, 23 mo), 1 of 10 patients had died of disease, and 2 others had tumor recurrence. All four patients with metastases, recurrences, and/or death from disease had serosal involvement at presentation (P = .02). Loss of heterozygosity of chromosome 11q was present in 25% of goblet cell carcinoids, 14% of ileal carcinoid tumors, and 9% of nonileal carcinoid tumors; of chromosome 16q in 38%, 29%, and 0 (P = .02); and of chromosome 18q in 56%, 86%, and 9% (P = .002), respectively. No mutations of K-ras, β-catenin, or DPC4 genes; p53 overexpression; or loss of staining for DPC4 was present in any tumors. These findings suggest that allelic loss of chromosomes 11q, 16q, and 18q in goblet cell carcinoids and ileal carcinoids may have an important role in the pathogenesis of these tumors.

Original languageEnglish (US)
Pages (from-to)1189-1198
Number of pages10
JournalModern Pathology
Volume16
Issue number12
DOIs
StatePublished - Dec 2003
Externally publishedYes

Fingerprint

Carcinoid Tumor
Appendix
Loss of Heterozygosity
Chromosomes
Catenins
Neoplasms
Neoplasm Metastasis
Recurrence
Serous Membrane
Neuroendocrine Tumors
Viscera
Genes
Lymph Nodes
Immunohistochemistry
Staining and Labeling
Mutation

Keywords

  • β-Catenin
  • 11q
  • 16q
  • Appendix
  • DPC4
  • Goblet cell carcinoid
  • K-ras
  • Loss of heterozygosity of 18q
  • p53

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Genetic Alterations in Goblet Cell Carcinoids of the Vermiform Appendix and Comparison with Gastrointestinal Carcinoid Tumors. / Stancu, Mirela; Wu, Tsung Teh; Wallace, Charita; Houlihan, Patrick S.; Hamilton, Stanley R.; Rashid, Asif.

In: Modern Pathology, Vol. 16, No. 12, 12.2003, p. 1189-1198.

Research output: Contribution to journalArticle

Stancu, Mirela ; Wu, Tsung Teh ; Wallace, Charita ; Houlihan, Patrick S. ; Hamilton, Stanley R. ; Rashid, Asif. / Genetic Alterations in Goblet Cell Carcinoids of the Vermiform Appendix and Comparison with Gastrointestinal Carcinoid Tumors. In: Modern Pathology. 2003 ; Vol. 16, No. 12. pp. 1189-1198.
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abstract = "Goblet cell carcinoid is a relatively rare neuroendocrine tumor of the vermiform appendix with poorly understood molecular pathogenesis. We studied the clinicopathologic features and genetic alterations, including allelic loss of chromosomes 11q, 16q, and 18q; sequencing of the K-ras, β-catenin, and DPC4 (SMAD4) genes; and p53 overexpression and loss of DPC4 by immunohistochemistry; in 16 goblet cell carcinoids. We compared the allelic loss in goblet cell carcinoids to those in 18 gastrointestinal carcinoid tumors. For goblet cell carcinoids, appendiceal perforation was the most common (70{\%}, 7/10) clinical presentation. The mean tumor size was 2.0 ± 1.5 cm (range, 0.4 to 4.5 cm). The tumor invaded to appendiceal serosa in 50{\%} (8/16) of patients, and two patients had metastasis in lymph nodes or adjoining viscera. With mean follow-up of 24 ± 14 months (median, 23 mo), 1 of 10 patients had died of disease, and 2 others had tumor recurrence. All four patients with metastases, recurrences, and/or death from disease had serosal involvement at presentation (P = .02). Loss of heterozygosity of chromosome 11q was present in 25{\%} of goblet cell carcinoids, 14{\%} of ileal carcinoid tumors, and 9{\%} of nonileal carcinoid tumors; of chromosome 16q in 38{\%}, 29{\%}, and 0 (P = .02); and of chromosome 18q in 56{\%}, 86{\%}, and 9{\%} (P = .002), respectively. No mutations of K-ras, β-catenin, or DPC4 genes; p53 overexpression; or loss of staining for DPC4 was present in any tumors. These findings suggest that allelic loss of chromosomes 11q, 16q, and 18q in goblet cell carcinoids and ileal carcinoids may have an important role in the pathogenesis of these tumors.",
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