Biomechanical remodeling of stroma by cancer-associated fibroblasts (CAF) in early stages of cancer is critical for cancer progression, and mechanical cues such as extracellular matrix stiffness control cell differentiation and malignant progression. However, the mechanism by which CAF activation occurs in low stiffness stroma in early stages of cancer is unclear. Here, we investigated the molecular mechanism underlying CAF regulation by SPIN90 and microtubule acetylation under conditions of mechanically soft matrices corresponding to normal stromal rigidity. SPIN90 was downregulated in breast cancer stroma but not tumor, and this low stromal expression correlated with decreased survival in breast cancer patients. deficiency facilitated recruitment of mDia2 and APC complex to microtubules, resulting in increased microtubule acetylation. This increased acetylation promoted nuclear localization of YAP, which upregulated expression of myofibroblast marker genes on soft matrices. depletion enhanced tumor progression, and blockade of microtubule acetylation in CAF significantly inhibited tumor growth in mice. Together, our data demonstrate that loss of SPIN90-mediated microtubule acetylation is a key step in CAF activation in low stiffness stroma. Moreover, correlation among these factors in human breast cancer tissue supports the clinical relevance of SPIN90 and microtubule acetylation in tumor development. .
The development of ectopic breast tissue is attributable to the failure of primitive mammary tissue to regress after the development of the mammary ridge, except at pectoral breast sites, and is most often evident in the axillae. Several benign and malignant breast diseases have been reported in ectopic axillary breast tissues. The most common cancerous pathology of ectopic breast tissue is invasive ductal carcinoma. Ectopic breast cancer presenting with simultaneous primary cancer of the pectoral breast is extremely rare. Herein, we report an invasive micropapillary carcinoma of an axillary ectopic breast, combined with a synchronous ductal carcinoma in situ in the contralateral pectoral breast of a 61-year-old woman.
Gelatinous degeneration of the bone marrow is rare, and its pathogenesis is unknown. A 61-year-old man with rectal cancer, who was treated successfully with surgery and chemotherapy 1 year ago, underwent 18F-FDG PET/CT for restaging, which showed a focal hot spot in the left scapula mimicking osseous metastasis. Excision bone biopsy revealed gelatinous degeneration of the bone marrow.
All breast cancers in lactating females in this study were observed on breast MR imaging despite the moderate-to-marked background parenchymal enhancement of lactating mammary tissue. Advances in knowledge: MR imaging can be used in the evaluation of disease extent and assessment of therapeutic response after neoadjuvant chemotherapy of breast cancer diagnosed during lactation.
Background: Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification. Methods: Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier). Results: On WHO classification, H&E staining exhibited 'fair agreement' (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems. Conclusions: Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.
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