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Expression of human paracrine hormones stanniocalcin 1 (STC1) and stanniocalcin 2 (STC2) may potentiate late breast cancer recurrence. We tested the hypothesis that expression of STC1 and STC2 in primary breast tumors is more strongly associated with late versus early recurrences. A total of 541 estrogen receptor-positive, tamoxifen-treated (ER/TAM) and 300 ER-negative, tamoxifen-untreated (ER/TAM) breast cancer patients who experienced recurrence within 10 years of primary diagnosis and matched recurrence-free controls were selected from a cohort of 11,251 Danish breast cancer patients diagnosed with stage I, II, or III breast cancer during 1985 to 2001. The association between IHC expression of STC1 and STC2 in primary breast tumor tissue microarrays and breast cancer recurrence was evaluated within median time to recurrence quintiles. The association between STC1 expression, dichotomized as positive or negative, and recurrence was strongly positive for the final time quintile (6-10 years postdiagnosis) in the ER/TAM group [aOR = 2.70; 95% confidence interval (CI): 1.22-5.98]. Regression of the log ORs relating dichotomous STC1 and STC2 expression to recurrence by median time to recurrence (year) resulted in a relatively large positive effect estimate for STC1 (β = 0.16; 95% CI, -0.03-0.36) and a near-null positive effect estimate for STC2 (β = 0.04; 95% CI, -0.14-0.21). Our results suggest a stronger association between primary tumor STC1 expression and late recurrence, as opposed to early recurrence, although no clear trend was apparent. STC1 expression in the primary tumor may potentiate late recurrences, suggesting dormancy pathways that merit further investigation. .

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Follicular lymphoma (FL) is an indolent neoplasia comprising approximately 20% of lymphomas. FL is generally considered incurable, with a median survival exceeding 10 years. A subset of FL patients experiences histological transformation (HT) to a more aggressive lymphoma, resulting in markedly poorer clinical outcome, with a reduced median survival after transformation of 1-2 years. Early, reliable prediction of HT would be valuable in the clinical setting, allowing pre-emptive therapeutic intervention. We previously used proteomics to identify the glycolytic enzymes fructose-bisphosphate aldolase A (aldolase A) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as candidate predictors of FL transformation. Now, we use immunohistochemistry to evaluate expression of these enzymes in paired primary FLs from patients with (n = 41) or without subsequent HT (n = 49), to test their value as predictive biomarkers. At initial FL diagnosis, patients with subsequent HT had significantly higher expression of aldolase A and GAPDH (p<0.001 and p<0.01) compared with patients without HT. Furthermore, high expression of aldolase A and GAPDH was associated with significantly shorter transformation free survival (p = 0.018, p = 0.001). These data suggest that high expression of aldolase A and GAPDH, may indicate increased metabolic turnover, and that these enzymes may be useful biomarkers in primary FL for predicting the risk of subsequent lymphoma transformation.