title: The Expression of Cohesin Subunit SA2 Predicts Breast Cancer Survival.
abstract: Cohesin is one of the main regulators of sister chromatid separation during the metaphase/anaphase transition. It is a multiprotein complex consisting of 4 core subunits, one of those being the SA2 subunit. SA2 plays the final role in dismantling the cohesion complex from the sister chromatids and also functions in DNA double-strand break repair and gene regulation. There is increasing evidence regarding the involvement of both overexpression and underexpression of cohesin in cancer. Here, we present expression patterns of SA2 in different types of human breast tissue, and the prognostic analysis in the material from breast cancer patients with long-term follow-up. SA2 immunoexpression was evaluated in benign, precancerous, and malignant breast tissue, and was classified into low-intensity or high-intensity groups. The DNA content was determined by image cytometry on breast cancer cell imprints. Prognostic analyses were based on 445 breast cancer patients with upto 20 years' follow-up. SA2 immunoexpression was equally high in both benign and precancerous breast tissue. Instead, 72% of the invasive breast cancers showed deficient SA2 expression. These patients were also associated with an unfavorable outcome as indicated by a 1.6-fold risk of breast cancer death (P=0.0208). The majority (75%) of the patients with low SA2 expression were alive 6.0 years after the diagnosis, whereas the majority of the patients with high SA2 expression survived 17.6 years after the diagnosis. No statistically significant association could be detected between SA2 immunoexpression and DNA aneuploidy. Our results and previous literature indicate that decreased SA2 immunoexpression is associated with malignant breast disease and a particularly unfavorable course of disease.
authors.affiliation: *Department of Pathology, University of Turku and Turku University Hospital †Department of Medical Statistics, Medical Faculty, University of Turku, Turku ‡Department of Pathology, Jyväskylä Central Hospital, Jyväskylä §Department of Pathology, Pori Central Hospital, Pori, Finland.
authors.forename: Heli
authors.initials: H
authors.lastname: Repo
authors.forename: Eliisa
authors.initials: E
authors.lastname: Löyttyniemi
authors.forename: Marjukka
authors.initials: M
authors.lastname: Nykänen
authors.forename: Minnamaija
authors.initials: M
authors.lastname: Lintunen
authors.forename: Henna
authors.initials: H
authors.lastname: Karra
authors.forename: Reino
authors.initials: R
authors.lastname: Pitkänen
authors.forename: Mirva
authors.initials: M
authors.lastname: Söderström
authors.forename: Teijo
authors.initials: T
authors.lastname: Kuopio
authors.forename: Pauliina
authors.initials: P
authors.lastname: Kronqvist
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D000097722:Cohesins