Loss of Heterozygosity on Chromosome 11p15 during Histological Progression in Microdissected Ductal Carcinoma of the Breast

Abstract

Microdissection of histologically identifiable components from formalin-fixed, paraffin-embedded tissue sections allows molecular genetic analyses to be correlated directly with pathological findings. In this study, we have characterized loss of heterozygosity (LOH) at chromosome 11p15 at different stages of progression in microdissected tumor components from 115 ductal carcinomas of the breast. Microdissected foci of intraductal, infiltrating, and metastatic tumors were analyzed to determine the stage of progression at which LOH at 11p15 occurs. LOH was detected in 43 (37%) of 115 cases. Foci of intraductal carcinoma could be microdissected from 85 cases, of which 30 (35%) showed LOH at some stage of progression. LOH was detected in the intraductal component in 26 of these 30 cases. Interstitial deletions were characterized by using a panel of 10 highly polymorphic markers. The smallest region of overlap (SRO) for LOH at 11p15 was bounded by the markers D11S4046 and D11S1758. LOH at 11p15.5 showed no correlation with estrogen receptor status, the presence of positive lymph nodes, tumor size, histological grade, or long-term survival. We conclude that 11p15 LOH usually occurs early in breast cancer development but less frequently does not develop until the infiltrating or metastatic stages of tumor progression.

Genetic Heterogeneity in Ductal Carcinoma of the Breast

“…Foci of intraductal, invasive, and metastatic carcinoma were identified and microdissected from 115 cases of breast cancer from the archives of the Armed Forces Institute of Pathology (Lichy et al, 1998). Each microdissected specimen was analyzed for LOH at a panel of microsatellite markers chosen from genetic loci previously shown to exhibit high frequency LOH in breast cancer (Aldaz et al, 1995;Brenner and Aldaz, 1997;Callahan et al, 1992).…”

A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13–15, a region subject to LOH and rearrangement in human carcinoma cell lines

“…Finally, we have localized ELF5 to human chromosome 11p13 ± 15, a region which undergoes loss of heterozygosity (LOH) in many types of cancer, such as ductal breast carcinoma (Lichy et al, 1998), lung carcinoma (Iizuka et al, 1995), rhabdoid tumor of the kidney (Hirose et al, 1996), prostate carcinoma (Kawana et al, 1997;Dahiya et al, 1997), gastric carcinoma (Ba a et al, 1996), and ovarian carcinoma . This region is believed to harbor several tumor suppressor genes (Ba a et al, 1996;Coleman et al, 1997;Feinberg, 1996;Gao et al, 1997;Ichikawa et al, 1996;Iizuka et al, 1995;Zenklusen et al, 1995), based upon both LOH data and the ability to inhibit the tumorigenicity in chemically induced murine squamous cell carcinomas upon introduction of human chromosome 11 (Zenklusen et al, 1995).…”

“…The markers most tightly linked to ELF5 are D11S3990 (6.5cR) and D11S3998 (15.9cR) (lod score43.0), and these markers are located in the region of 11p13 ± 15 (Figure 3). This chromosomal region frequently undergoes loss of heterozygosity (LOH) in several types of carcinoma (Ba a et al, 1996;Dahiya et al, 1997;Hirose et al, 1996;Iizuka et al, 1995;Kawana et al, 1997;Lichy et al, 1998;Wilson et al, 1996).…”

Classic Kaposi Sarcoma in the United States over the last two decades: A clinicopathologic and molecular study of 438 non-HIV-related Kaposi Sarcoma patients with comparison to HIV-related Kaposi Sarcoma

“…DNA was extracted from six 6-m sections of each block by deparaffinization with Hemo-De followed by protease K digestion, extraction with phenol/ chloroform, and ethanol precipitation, as previously described by Lichy et al 5 The probe and primer sequences are listed in Table 1.…”