These data corroborate the involvement of three lncRNAs (HOTAIR, H19 and KCNQ1OT1) in breast tumourigenesis and support lncRNA CISH as a potential clinical assay. Importantly, CISH allows identification of the tissue compartment expressing lncRNA.
Plasmacytoid urothelial carcinoma is a rare form of invasive urothelial carcinoma first described in 1991 by Sahin et al. [Acta Cytol 1991;35:277-280]. Since this original publication, over 70 cases of plasmacytoid urothelial carcinoma have been described. A small number of cytologic descriptions have been published, including cases involving cerebrospinal fluid cytology, bladder washings and urine cytology. To our knowledge, we describe the first fine needle aspiration of metastatic plasmacytoid urothelial carcinoma in a 75-year-old man who presented with a pathologic fracture of the L4 vertebral body. One of the diagnostic pitfalls in the cytologic evaluation of this rare malignancy is the positive staining with CD138. While CD138 is a marker for plasma cell differentiation, it is also positive in plasmacytoid urothelial carcinoma. In addition to recognizing the cytomorphologic details, a full immunohistochemical panel is helpful in properly characterizing this entity. A brief discussion of long-term prognosis and treatment benefit is provided.
Liver resection for metastatic cancer has become the standard of care for specific groups of patients, including noncolorectal non-neuroendocrine liver metastases (NCNNELM). Liver metastasis from differentiated thyroid carcinoma is considered rare, with an approximated frequency of 0.5%. We present a case of metastatic papillary thyroid carcinoma (PTC) to the liver and literature review. Herein, we report a 72-year-old male that underwent formal left hepatectomy for 4.4 cm metastatic PTC generating left bile duct obstruction. Two months after, presented with multiple small lesions within the hepatic parenchyma and diffuse ductal dilatation of the right biliary system. Therefore, treated with a percutaneous biliary drain placement without complications. In a patient diagnosed with initial Stage II PTC, undergoing total thyroidectomy 10 years before presenting to the clinic. Bearing over a decade of treatments for local and distal recurrences. We believe approaching strategies for this specific disease should be developed to establish standard management.
Background: Long non-coding RNAs (lncRNAs) participate in a spectrum of biological activities by diverse mechanisms. LncRNA dysregulation has been reported for many cancers. Some lncRNAs may function as oncogenes (OG) and others as tumor suppressor genes (TSG). To date, lncRNA has been investigated primarily by qRT-PCR. In this study we have examined the relationship of lncRNA expression patterns to breast tumor pathology by chromogenic in situ hybridization (CISH). Methods: Expression of six lncRNAs, HOTAIR (OG), H19 (OG), Kcnq1ot1 (OG), Meg3 (TSG), Malat1 (OG), and ZFas1 (TSG), plus HER2 and MKI67 mRNAs was examined by RNAscope® CISH using tissue microarrays (TMAs) comprising normal epithelia, ductal carcinoma in situ (DCIS), and invasive carcinoma (IC) from 45 patients. HOTAIR/H19-mediated protein EZH2 was evaluated by immunohistochemistry (IHC). CISH and IHC results were scored in terms of the percentage of stained cells (<2%=0, 2-10%=1, 10-50%=2, >50%=3) and staining intensity (low=1, medium=2, high=3). Staining grade (SG) values were calculated as SG= proportion x intensity (SG value range=1-9). Results: The TMAs contained 36 normal epithelia (N), 34 DCIS (D) and 43 IC tissue punches. HOTAIR expression was common: at SG≥1, expression was detected in N:85%; D:97%; IC:100% (p>0.05). HOTAIR SG mean values (N 4.0, D 5.7, IC 6.2) were significantly higher in DCIS and IC than in normal tissues (N:D p<0.05; N:IC p<0.01; D:IC p>0.05). IC HOTAIR SGs correlated with Nottingham grade (p<0.01), HER2 CISH (p<0.01) and MKI67 CISH (p<0.05). HOTAIR expression levels in DCIS were associated with MKI67 CISH (p<0.01). H19 was rarely expressed in normal epithelial or tumor cells but was strongly expressed especially in inter-lobular stromal cells around invasive growths. At SG≥1 H19 was detected in N:38%; D:55%; IC:90% (p<0.01). H19 SG means (N 1.3, D 2.3, IC 3.7) were significantly higher among IC than normal or DCIS tissues (N:D p>0.05; N:IC p<0.01; D:IC p<0.05). IC H19 expression showed a positive correlation with Nottingham grade (p<0.05) and with MKI67 expression (p<0.01). H19 in DCIS showed a correlation with MKI67 CISH (p<0.01). Kcnq1ot1 staining was more common in DCIS and IC than in normal tissues: at SG≥1, N:77%; D:96%; IC:94% (p<0.01). Both the DCIS and IC SGs correlated with MKI67 expression (p<0.05). Meg3 expression was associated with normal breast; at SG≥1, N:46%; D:2%; IC:0%, [p<0.01]). Malat1 stained strongly in all cells in all specimens. Zfas1 specimen staining was absent or weak. IC and DCIS EZH2 IHC staining correlated positively with both HOTAIR and H19 expression (p<0.05). Conclusions: These data demonstrate the utility of CISH for investigating and demonstrating pathologic lncRNA expression. HOTAIR and H19 in particular and possibly Kncq1ot1 and Meg3 are potential breast cancer biomarkers. H19 may be a marker for DCIS at increased risk of progression to invasive cancer. Citation Format: Zhouwei Zhang, Zhihua Peng, Daniel Olsen, James deKay, Donald L. Weaver, Mark F. Evans. Long non-coding RNA in situ hybridization signal patterns correlate with breast tumor pathology. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1498. doi:10.1158/1538-7445.AM2014-1498
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