[1891] Assessment of CGH-Array Usefulness in Metachronous Tumors

Francois Le Loarer, Pauline Lagarde, Agnes Neuville, Jean Michel Coindre, Frederic Chibon. Rouen University Hospital, Rouen, France; Institut Bergonié, Bordeaux, France

Background: Poorly differentiated metachronous tumors challenge pathologists ability to distinguish confidently a recurrence of the first tumor from a distinct tumor event. Traditional approach is based upon conventional morphology supplemented by immunohistochemistry. The use of molecular tools on a routine basis has long been hindered by the requirement of frozen material. CGH-array protocols have been recently adapted to comply with formalin-fixed paraffin-embedded (FFPE) material. We assessed CGH array technical feasability and diagnostic utility in a series of metachronous tumors.
Design: We selected seven consecutive cases of metachronous malignancies submitted for expert review from December 2010 to April 2011. In all cases, the second event was a poorly differentiated sarcomatoid malignant tumor. CGH-array was performed on Agilent platform with 60k oligo-array. The molecular biologist compared blindly the genomic profiles of couples of metachronous tumors to render a diagnosis of recurrence of the first tumor or distinct tumor events.
Results: Two out of seven cases provided poor quality genomic DNA precluding confident CGH analysis. Technical limitations were due to cellularity of one specimen and poor quality fixation step in the other one. Apart these limitations, we reached high quality CGH-array analysis equivalent to frozen sample-based analysis. Genomic-based diagnoses were in accordance with morphology in three cases out of five and contradicted morphology in one case. No definitive genomic diagnosis could be rendered in one case.

Cases review

Gender - Age*	Primary site	Date of primary	Diagnosis of primary	Second site	Histologic diagnosis	Genomic analysis
female 63	maxilla	2010	sarcomatoid carcinoma	adrenal gland	metastasis	same tumor
male 56	kidney	2000	clear cell carcinoma	maxilla	pleomorphic sarcoma	distinct tumor
male 70	tongue	2004	squamous carcinoma	gengiva	recurrence of carcinoma	distinct tumor
female 61	meninges	2007	meningioma	adrenal gland	metastasis	same tumor
male 69	cervical lymph node	2008	squamous carcinoma	breast	metastasis	NA
female 68	kidney	2008	papillary carcinoma	humerus	metastasis	NA
male 76	kidney	2007	papillary carcinoma	liver	metastasis	uncertain

* age at the primary


Conclusions: According to our results, CGH-array can be fully applied to FFPE material. The technical caveats we met were due to fixation step and cellularity of the sample, emphasizing the need for pre-analytic step standardization. A larger scale use of CGH-array would require further reflection upon the appropriate manner to analyse genomic profiles. We are committed to assess this issue on a larger series.
Category: Special Category - Pan-genomic/Pan-proteomic approaches to Cancer

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 280, Tuesday Morning