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ampullary adenocarcinoma

Tuesday 30 November 2010

invasive ampullary adenocarcinoma; adenocarcinomas of the ampulla of Vater

Definition: Ampullary adenocarcinoma (A-AC) is a rare malignancy arising from the ampulla of Vater.

Ampullary adenocarcinomas (A-ACs) are rare malignancies with considerable importance because of their high curable resection rate and improved survival rate among periampullary cancers.

Prognosis parameters

- tumoral budding

  • Tumor budding is frequently encountered in AAC.
  • High-budding is a strong independent predictor of overall survival, with a prognostic correlation stronger than the 2 established parameters: T-stage and lymph node metastasis.
  • Therefore, budding should be incorporated into surgical pathology reports for AAC.

Molecular pathology

- KRAS mutations

  • KRAS mutation is detected in 30-40% of patients with A-AC.
  • KRAS mutation is a partial prognostic factor in ampullary adenocarcinoma
  • A meta-analysis indicates that KRAS mutation is associated with poor RFS, but not with OS in patients with A-AC. (27517148)

- Low incidence of KRAS, BRAF, and PIK3CA mutations in adenocarcinomas of the ampulla of Vater (26997442)

- The RAS-RAF-MAPK pathway is involved in the development of A-ACs and is a potential therapeutic target.

  • In a study, of 62 A-ACs, 30.6% had KRAS mutations, but no BRAF mutations and low frequency (1.6%) of PIK3CA mutation were detected. (26997442)
  • KRAS mutation was correlated with poor tumor differentiation and was a predictor of shorter recurrence-free survival period in overall A-ACs, whereas the prognosis according to the histologic subtypes was not affected by KRAS mutation.
  • Lymph node metastasis was an independent prognostic factor of poor overall survival. Intestinal- and pancreatobiliary-type A-ACs had similar prognosis.
  • Intestinal- and pancreatobiliary-type A-ACs had different prognostic factors; tumor differentiation and lymph node metastasis strongly predicted overall survival and recurrence-free survival in pancreatobiliary-type tumors, respectively, whereas no independent prognostic factors were demonstrated for intestinal-type tumors.
  • Low incidence of KRAS mutations and their strong prognostic value in A-ACs may suggest the potential of survival benefit depending on the epidermal growth factor receptor-targeted therapy. (26997442)
  • Much lower frequencies of BRAF and PIK3CA mutations may suggest that they do not play a major role in the tumorigenesis of A-ACs.

References

- Tumor budding as a strong prognostic indicator in invasive ampullary adenocarcinomas. Ohike N, Coban I, Kim GE, Basturk O, Tajiri T, Krasinskas A, Bandyopadhyay S, Morohoshi T, Shimada Y, Kooby DA, Staley CA, Goodman M, Volkan Adsay N. Am J Surg Pathol. 2010 Oct;34(10):1417-24. (20871215)