Loss of heterozygosity on chromosome 16q suggests malignancy in core needle biopsy specimens of intraductal papillary breast lesions

Abstract

It is often difficult to make a definitive diagnosis of papillary breast lesions using core needle biopsy (CNB) specimens. We studied loss of heterozygosity (LOH) on chromosome 16q in order to assess its diagnostic use for papillary breast lesions in CNB specimens. Of 25 patients with intraductal papillary breast tumors, we extracted DNA from paired samples of tumor cells from CNB specimens and non-tumor cells from subsequent excision specimens and analyzed LOH at the D16S419 and D16S514 loci on chromosome 16q. LOH analysis results were compared with final diagnoses based on pathological features of the resected specimens. On the CNB specimens, 21 tumors were histologically diagnosed as indeterminate or suspicious for malignancy, while four tumors were unambiguously malignant. Of the 21 indeterminate or suspicious tumors, 11 were finally diagnosed as benign and ten as malignant, and on these, LOH analyses were informative for 8 of the 11 benign tumors and 7 of the 10 malignant tumors. LOH was also informative on two of the four tumors unambiguously malignant on CNB. None of the eight informative benign tumors showed LOH on 16q. Six of the eleven informative malignant tumors showed LOH on 16q. LOH on 16q was significantly different between CNB specimens of benign and malignant intraductal papillary tumors (P = 0.007). Analysis of LOH on 16q may be helpful in making a definitive diagnosis in cases of papillary breast lesions, in both excised and CNB specimens.

Pathological criteria and practical issues in papillary lesions of the breast – a review

“…A high frequency of loss of heterozygosity (LOH) at chromosome 16p13 and 16q21 was detected both in intraductal papillomas and papillary carcinomas, whereas LOH at locus 16q23 was limited to malignant lesions. LOH at the TP53 locus is also significantly associated with the malignant phenotype . Additionally, a higher PIK3CA or AKT mutation frequency was identified in papillomas than in papillary carcinomas, indicating that papillomas could be driven by mutations in the PIK3CA–AKT pathway, whereas papillary carcinomas might develop along a molecular pathway that is somewhat divergent from that of most benign papillary proliferations …”

Collagen Type XI Alpha 1 Expression in Intraductal Papillomas Predicts Malignant Recurrence

“…Markers as the CD44 [ 37 ] or cyclin D1 [ 38 ] have been proposed as differentially expressed genes between malignant and benign papillary lesions, but there is no correlation with malignant recurrence of intraductal papillomas. Some genetic alterations, such as loss of heterozygosity of chromosome 16 [ 39 ], have also been proposed as capable of predicting an increased susceptibility for malignant recurrence of intraductal papillomas, but accuracy has not been demonstrated [ 38 , 39 ].…”

Papillary lesions of the breast

“…They share some genetic alterations found in low-grade DCIS of other architecture. Studies of papillary breast lesions including invasive papillary carcinomas revealed LOH at loci 16q12.2, 16q21, and 16q23, but LOH at the TP53 locus only in malignant papillary lesions [24,93].…”