[1862] Loss of Heterozygosity (LOH) at 17p13 and 22q13 Is Associated with Metastasis and Shared by Breast and Thyroid Carcinomas

Bing Zhu, Sydney D Finkelstein, Jan F Silverman, Stephen M Rohan, Xiaoqi Lin. Northwestern University, Chicago, IL; RedPath Integrated Pathology, Inc., Chicago, IL; Allegheny General Hospital, Chicago, IL

Background: Our previous studies have revealed that LOHs at a few specific chromosomal loci are involved in metastasis of breast ductal carcinoma (BDC) and papillary thyroid carcinoma (PTC). In this study, we compared the patterns of LOH involved in metastasis of BDC and PTC.
Design: We retrieved 14 BDC cases with known metastasis and 19 BDC cases without metastasis as well as 12 PTC cases with metastasis and 14 cases without metastasis. Analysis of 17 polymorphic microsatellite repeat markers (PMRM) targeting 1p34-36, 3p24-26, 5q23, 9p21, 10q23, 17p13, 17q12, 17q21, 21q22, and 22q13 was performed on DNA isolated from primary tumors.
Results: See Table 1 and 2.

Table 1. LOHs in BDCs with or without metastasis.
ChromosomePMRM+ Metastasis*- Metastasis*P Value
1p34-36D1S-14/92/150.039
 D1S-23/114/15 
3p24-26D3S-16/123/13 
 D3S-26/102/11 
5q23D5S-13/113/14 
 D5S-21/102/14 
9p21D9S-15/103/17 
 D9S-25/114/16 
10q23D10S-13/115/14 
 D10S-23/101/13 
17p13D17S-15/113/15 
 D17S-24/111/130.014
17q12D17S-34/8  
 D17S-43/8  
17q21D17S-55/117/13 
21q22D21S-13/111/120.036
22q13D22S-15/111/11 
Yates' correction test. Cases with mutation/cases with informative markers.



Table 2. LOHs in PTCs with or without metastasis.
Chromosome+ Metastasis- MetastasisP Value
1p367/125/14 
3p242/124/14 
3p120/123/114 
7p310/122/14 
9p216/128/14 
10q236/123/140.017
17p133/121/140.003
17q214/121/14< 0.001
18q211/123/14 
21q223/123/14 
22q136/123/140.017
Yates' correction test.


Conclusions: 1. LOH at 1p34-36, 17p13 and 22q13 is significantly more common in BDC with metastasis compared to BDC without metastasis.
2. LOH at 10q23, 17p13, 17q21, and 22q13 is significantly more common in PTC with metastasis compared to PTC without metastasis.
3. LOH at 17p13 and 22q13 is shared by both BDC and PTC with metastasis, whereas LOH at 1p34-36 in BDC and LOHs at 10q23 and 17q21 is not shared.
4. Therefore, our results suggest that BDC and PTC share the same metastatic mechanisms that involve LOH at 17p13 and 22q13. The LOH signature may be clinically useful to better predict which carcinomas (breast and thyroid) might metastasize. More detailed studies to identified genes in these shared regions of LOH may provide insight into molecular mechanism of metastasis in these two tumor types.
Category: Pathobiology

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 284, Monday Morning

 

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