Microdissection Genotyping Analysis of the Effect of Intraarterial Cytoreductive Chemotherapy in the Treatment of Lacrimal Gland Adenoid Cystic Carcinoma
Accepted 1 September 2005. published online 11 November 2005.
Purpose
To investigate the feasibility of integrating molecular analysis into standard histopathology for lacrimal gland adenoid cystic carcinoma (ACC), and to gain insights into the molecular pathogenesis of this tumor and its response to intraarterial cytoreductive chemotherapy (IACC) that is of clinical use.
Design
A retrospective, comparative case series.
Methods
setting: Institutional. patient population: Nine consecutive patients with lacrimal gland ACC were treated with IACC, followed by orbital exenteration and chemoradiotherapy. This case series was compared with a series of seven patients treated by conventional local therapies. intervention procedure: Gene analysis was performed on microdissected tissue samples. Mutational allelotyping targeting nine genomic loci was performed with 15 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes serving as markers for the presence of gene deletion. main outcome measure: A fractional mutation index was used to compare the acquired mutational load between different tumors having nonidentical patterns of microsatellite informativeness.
Results
Allelic imbalance (loss of heterozygosity [LOH]) for microsatellite markers at 1p36 was the single most common site affected by imbalance in this series, followed by LOH in temporal sequence involving 9p21, 22q12, 10q23, and 9q22.
Conclusions
Microdissection genotyping holds promise as a clinical tool in integrating molecular analysis into standard histopathology to advance the understanding of lacrimal gland ACC tumorigenesis. A unique time course for temporal mutation acquisition in ACC is proposed, consisting of 1p36 loss first. Allelic loss for microsatellite markers at 1p36 may be a common as well as an early event in ACC formation and progression.
aDepartment of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida
bDepartment of Internal Medicine, University of Miami Miller School of Medicine, Miami, Florida
Inquiries to David T. Tse, MD, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17th Street, Miami, FL 33136; fax: (305) 326-6443
See accompanying Article on page 44 and Brief Report on page 187.
Supported in part by NIH center grant P30-EY014801; an unrestricted grant from Research to Prevent Blindness Inc, New York, New York, and a grant from the Plum Foundation, Los Angeles, California.
This manuscript is based on a thesis that was prepared in partial fulfillment of the requirements for membership in the American Ophthalmological Society.
ABSTRACT