A series of 82 consecutive cases of mucinous carcinomas of the female breast was investigated for their clinical, morphological, and histochemical features and for the influence of some tumor characteristics on its prognosis. Two groups, a "pure" subtype (n = 58) and a "mixed" subtype (n = 24), were considered, according to the absence or the presence of concomitant areas with typical infiltrating ductal carcinoma. Eighty patients were followed with an average of 7.4 years. The actuarial survival was 58.5% at 10 years. The group of pure mucinous carcinomas showed a statistically significant better prognosis (P = 0.0007) than that of the group of mixed tumors, as well as a lower percentage of axillary nodal metastasis. Tumor dimension of both pure and mixed mucinous carcinomas influenced the prognosis, since patients with T1 tumors had longer survival than those with T2 tumors (P = 0.05) and the latter showed less mortality than T3 tumor cases (P = 0.036). Node-negative patients also had a more favorable outcome with lower mortality than node positive patients (P = 0.007). None of the T1 pure mucinous carcinomas had axillary metastasis, which may have implications for the surgical protocols. The evaluation of quantitative and qualitative content in mucosubstances did not correlate with the prognosis. However, sulfomucins were demonstrated in 30.5% of cases; this fact points to add breast carcinoma to the group of neoplasms that may present as a metastatic sulfomucin-producing adenocarcinoma.
Brito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Mitochondria provide the first line of defense against the tumor-promoting effects of oxidative stress. Here we show that the prostate-specific homeoprotein NKX3.1 suppresses prostate cancer initiation by protecting mitochondria from oxidative stress. Integrating analyses of genetically engineered mouse models, human prostate cancer cells, and human prostate cancer organotypic cultures, we find that, in response to oxidative stress, NKX3.1 is imported to mitochondria via the chaperone protein HSPA9, where it regulates transcription of mitochondrial-encoded electron transport chain (ETC) genes, thereby restoring oxidative phosphorylation and preventing cancer initiation. Germline polymorphisms of NKX3.1 associated with increased cancer risk fail to protect from oxidative stress or suppress tumorigenicity. Low expression levels of NKX3.1 combined with low expression of mitochondrial ETC genes are associated with adverse clinical outcome, whereas high levels of mitochondrial NKX3.1 protein are associated with favorable outcome. This work reveals an extranuclear role for NKX3.1 in suppression of prostate cancer by protecting mitochondrial function.
Significance:
Our findings uncover a nonnuclear function for NKX3.1 that is a key mechanism for suppression of prostate cancer. Analyses of the expression levels and subcellular localization of NKX3.1 in patients at risk of cancer progression may improve risk assessment in a precision prevention paradigm, particularly for men undergoing active surveillance.
See related commentary by Finch and Baena, p. 2132.
This article is highlighted in the In This Issue feature, p. 2113
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