Allelic loss on chromosome 1p is associated with progression and lymph node metastasis of primary breast carcinoma.

Background: Frequent allelic losses on the short arm of chromosome 1 have been observed in a wide variety of human tumors. Cytogenetic and molecular genetic studies in breast carcinomas have shown frequent alterations on chromosome 1, involving loss of 1p or gain of 1q.

Methods: To define the locations of tumor suppressor genes, 143 primary breast carcinomas were examined for allelic loss using 15 highly polymorphic microsatellite markers on 1p. Correlations also were sought between allelic loss on 1p and several clinicopathologic parameters.

Results: Allelic loss was observed in 73 of the tumors (51%). Detailed deletion mapping identified target regions at 1p36, 1p34-p35, and 1p22-p31. Allelic losses at 1.36 or 1p34-p35 were observed more frequently in tumors of the solid tubular and scirrhous types than in less aggressive histologic types. Conversely, allelic loss at 1p22-p31 was correlated with lymph node metastasis and a tumor size > 2 cm.

Conclusions: Inactivation of tumor suppressor genes that lie in either 1p36 or 1p34-p35 might affect carcinogenic mechanisms in a histologic type specific manner, especially the solid tubular and scirrhous types. Alterations of one or more tumor suppressor genes at 1p22-p31 may play a role at late stages of breast carcinogenesis, especially with regard to local progression and lymph node metastasis.