Most cancer patients with solid tumors who succumb to their illness die of metastatic disease. While early detection and improved treatment have led to reduced mortality, even for those with metastatic cancer, some patients still respond poorly to treatment. Understanding the mechanisms of metastasis is important to improve prognostication, to stratify patients for treatment, and to identify new targets for therapy. We have shown previously that expression of nephronectin (NPNT) is correlated with metastatic propensity in breast cancer cell lines. In the present study, we provide a comprehensive analysis of the expression pattern and distribution of NPNT in breast cancer tissue from 842 patients by immunohistochemical staining of tissue microarrays from a historic cohort. Several patterns of NPNT staining were observed. An association between granular cytoplasmic staining (in <10% of tumor cells) and poor prognosis was found. We suggest that granular cytoplasmic staining may represent NPNT-positive exosomes. We found that NPNT promotes adhesion and anchorage-independent growth via its integrin-binding and enhancer motifs and that enforced expression in breast tumor cells promotes their colonization of the lungs. We propose that NPNT may be a novel prognostic marker in a subgroup of breast cancer patients.

Conflict of interestThe authors report no conflicts of interest. Word count: 3979 Number of tables: 3 Number of figures: 3 Number of supplementary tables: 5Number of supplementary figures: 3 3 Molecular subtypes of breast cancer: long-term incidence trends and prognostic differences.Background: Secular trends in incidence and prognosis of molecular breast cancer subtypes are poorly described. We studied long-term trends in a population of Norwegian women born 1886-1977.Methods: A total of 52 949 women were followed for breast cancer incidence, and 1423 tumours were reclassified into molecular subtypes using immunohistochemistry and in situ hybridization. We compared incidence rates among women born 1886-1928 and 1929-1977, estimated age-specific incidence rate ratios (IRRs), and performed multiple imputations to account for unknown subtype. Prognosis was compared for women diagnosed before 1995 and in 1995 or later, estimating cumulative risk of death and hazard ratios (HR). Conclusion:We found a strong secular incidence increase restricted to Luminal A and Luminal B (HER2-) subtypes, combined with a markedly improved prognosis for these subtypes and for the Basal phenotype.Impact: This study documents a clear secular increase in incidence and a concomitant improved prognosis for specific molecular breast cancer subtypes.. 4 Molecular subtypes of breast cancer: long-term incidence trends and prognostic differences.

IntroductionWe evaluated colposcopy in the routine diagnostic workup of women with abnormal cervical cytology, as well as the diagnostic value of endocervical curettage material and biopsies taken from colposcopy‐positive and colposcopy‐negative quadrants of the cervix.Material and methodsThis cross‐sectional study included 297 nonpregnant women with abnormal cervical cytology and no prior treatment for cervical dysplasia or cancer. All women underwent gynecological examination, colposcopy, endocervical curettage, and had cervical biopsies taken. Colposcopy was considered satisfactory if the squamocolumnar junction was fully visible, and biopsies were taken from all four quadrants of the cervix, regardless of colposcopy results.ResultsIn all, 130 of the women in our study had satisfactory colposcopy results and were diagnosed with cervical intraepithelial neoplasia grade 2 or worse (CIN2+), 61% via a colposcopy‐positive biopsy and 39% via a colposcopy‐negative biopsy. Eighty‐seven of them had positive colposcopy results, but CIN2+ was histologically verified from colposcopy‐positive biopsies in 91% (n = 79) and from colposcopy‐negative biopsies in 9% (n = 8). The remaining 43 women with CIN2+ had negative colposcopy findings, so their diagnosis was verified in colposcopy‐negative biopsies. The sensitivity of colposcopy alone to detect CIN2+ was 61% (95% CI 52–69).ConclusionsIn the present study, colposcopy was not a stand‐alone diagnostic method. Colposcopy‐negative biopsies had a clear additive value, identifying a substantial proportion of women with both positive and negative colposcopy results with treatment‐worthy cervical dysplasia. Endocervical curettage material had little diagnostic value in this study.

AR is an independent predictor of good prognosis in BC, particularly in grade 3 and Luminal A tumours. Discordant AR-expression between primary tumour and LNM was observed in 21.4% of cases and most often there was a switch from AR primary tumour to AR axillary LNM.

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