Glycodelin expression associates with differential tumour phenotype and outcome in sporadic and familial non-/ breast cancer patients

Laura C. Hautala (1, 2) , Dario Greco (1) , Riitta Koistinen (2) , Tuomas Heikkinen (1) , Päivi Heikkilä (3) , Kristiina Aittomäki (4) , Carl Blomqvist (5) , Hannu Koistinen (2) , Heli Nevanlinna (1)

1 Department of Obstetrics and Gynaecology
2 Department of Clinical Chemistry
3 Department of Pathology
4 Department of Clinical Genetics
5 Department of Oncology

Glycodelin (encoded by gene) is a secreted lipocalin protein mainly expressed in reproductive tissues, but also in several tumour types. In the breast, glycodelin is expressed both in normal epithelial and cancerous tissue. To investigate the association of glycodelin with clinicopathological features of breast cancer and outcome of patients we evaluated the protein expression of glycodelin in a large series of breast tumours. Immunohistochemical analysis of tissue microarrays was used to study glycodelin expression on 399 sporadic and 436 familial non-/ tumours with strong family history. Gene expression analysis was used to define genes co-expressed with in sporadic and familial non-/ breast tumours. In the sporadic series, the glycodelin expression associated with low proliferation rate ( < 0.001), with a tendency towards well-differentiated tumours (grades 1 and 2,  = 0.012) and high cyclin D1 ( = 0.034) expression. However, in familial non-/ cases with strong family history glycodelin expression associated with a less favourable phenotype, i.e. positive lymph node status ( = 0.003) and HER2-positive tumours ( = 0.009). Moreover, the patients with glycodelin-positive tumours had an increased risk for distant metastases ( = 0.001) and in multivariate analysis glycodelin expression was an independent predictor of metastasis (hazard ratio (HR) = 2.22, 95% confidence interval (95% CI) = 1.22-4.03,  = 0.009) in familial non-/ breast cancer. Gene expression analysis further revealed different gene expression profiles correlating with the expression in the sporadic and familial non-/ breast cancers. Our findings suggest differential progression pathways in the sporadic and familial non-/ breast tumours expressing glycodelin.

Mots clés: Breast cancer; Glycodelin; PAEP; Non-/; Familial breast cancer

Laura C. Hautala, Dario Greco, Riitta Koistinen, Tuomas Heikkinen, Päivi Heikkilä, et al.. Glycodelin expression associates with differential tumour phenotype and outcome in sporadic and familial non-/ breast cancer patients. Breast Cancer Research and Treatment, 2010, 128 (1), pp.85-95. ⟨10.1007/s10549-010-1065-y⟩. ⟨hal-00615368⟩