Microdissection genotyping analysis of the effect of intraarterial cytoreductive chemotherapy in the treatment of lacrimal gland adenoid cystic carcinoma.
OBJECTIVE
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.


METHODS
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.
Tse
David T
DT
Department of Ophthalmology, University of Miami-Miller School of Medicine, 900 NW 17th Street, Miami, FL 33136, USA. dtse@med.miami.edu
Finkelstein
Sydney D
SD
Benedetto
Pasquale
P
Dubovy
Sander
S
Schiffman
Joyce
J
Feuer
William J
WJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000235:genetics; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005134:Eye Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D007261:Infusions, Intra-Arterial; D007766:Lacrimal Apparatus Diseases / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D042282:Microdissection; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics; D009915:Orbit / Q000601:surgery; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins