Claudin-2 promotes breast cancer liver metastasis by enabling seeding and early cancer cell survival. We now demonstrate that Claudin-2 is functionally required for colorectal cancer liver metastasis and that Claudin-2 expression in primary colorectal cancers is associated with poor overall and liver metastasis-free survival. We have examined the role of Claudin-2, and other claudin family members, as potential prognostic biomarkers of the desmoplastic and replacement histopathological growth pattern associated with colorectal cancer liver metastases. Immunohistochemical analysis revealed higher Claudin-2 levels in replacement type metastases when compared to those with desmoplastic features. In contrast, Claudin-8 was highly expressed in desmoplastic colorectal cancer liver metastases. Similar observations were made following immunohistochemical staining of patient-derived xenografts (PDXs) that we have established, which faithfully retain the histopathology of desmoplastic or replacement type colorectal cancer liver metastases. We provide evidence that Claudin-2 status in patient-derived extracellular vesicles may serve as a relevant prognostic biomarker to predict whether colorectal cancer patients have developed replacement type liver metastases. Such a biomarker will be a valuable tool in designing optimal treatment strategies to better manage patients with colorectal cancer liver metastases.

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We report the case of a 39-year-old woman complaining of painless unilateral nipple enlargement for 3 weeks. She had no family history of breast cancer. Clinical examination revealed left nipple enlargement without pain, erythema, or skin changes m no associated palpable breast or axillary masses. Ultrasound showed several bright foci in the left nipple suggestive of microcalcifications. Neither solid nor cystic masses were detected. The mammogram performed subsequently confirmed the presence of multiple pleomorphic microcalcifications within the nipple. Wedge biopsy showed a syringomatous adenoma. Wide local excision of the nipple was performed. The postoperative course was uneventful.

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