Crown-like structures in breast adipose tissue of breast cancer patients: associations with CD68 expression, obesity, metabolic factors and prognosis.

Crown-like structures of the breast (CLS-B), defined by the clustering of macrophages (identified using CD68 immunohistochemical staining) to surround a dying adipocyte, are a sign of adipose-tissue inflammation. In human cohorts, CLS-B positively correlates with older age, obesity, dyslipidemia and higher levels of glucose, insulin, C-reactive protein and IL-6. In an existing cohort of early-stage breast cancer patients, CLS-B were identified using H&E stained histologic sections (hCLS-B), and by CD68 immunohistochemistry (CD68 + CLS-B). We examined associations of H&E and CD68-detected CLS-B with clinicopathologic features using χ2 tests, with metabolic factors using Wilcoxon rank sum tests and with disease free and overall survival using Cox regression models. hCLS-B were detected in 59 of 163 patients with slides (36.2%) and CD68 + CLS-B in 37 of 119 patients with paraffin blocks (31.1%). hCLS-B were positively correlated with higher weight (p = 0.003), BMI (p = 0.0008) and C-reactive protein (p = 0.045). CD68 + CLS-B were positively correlated with higher weight (p = 0.006), BMI p = 0.001), leptin (p = 0.034), insulin (p = 0.008) and Homeostasis Model Assessment (p = 0.027). CD68 + CLS-B were associated with poor distant disease-free with a hazard ratio (HR) of 2.81, 95% confidence interval (CI) 1.20-6.57, and overall survival with HR 3.97 (1.66-9.48), while hCLS-B were not associated with either: HR for distant recurrence 0.59 (0.26-1.30); HR for death 1.04 (0.50-2.16). The presence of hCLS-B and of CD68 + CLS-B were associated with obesity; CD68 + CLS-B were associated with insulin resistance and adverse prognosis. Similar patterns were not seen for hCLS-B. Research is needed to understand the biologic basis for these differences.

Combination of MCM2 With Ki67 and p16 Immunohistochemistry Can Distinguish Uterine Leiomyosarcomas.

Our objective was to evaluate the diagnostic utility of 2 new proliferation markers, cyclin D1 and minichromosome maintenance complex component 2 (MCM2), in comparison with p16, p53, and Ki67 in differentiating the spectrum of smooth muscle tumors. An institutional database search from 2009 to 2017 identified 10 cases of uterine leiomyoma with bizarre nuclei (LBN), 12 smooth muscle tumors of uncertain malignant potential, and 13 leiomyosarcomas (LMS). Ten resected leiomyomas (LM) were included as controls. Immunohistochemistry was performed on the befitting representative block from each case. Ki67 was <10% in all LMs and LBNs, whereas >10% in all LMSs. Although wild-type in majority of cases, p53 was overexpressed in 38% of LMSs. Cyclin D1 nuclear positivity in LMs, LBNs, and smooth muscle tumors of uncertain malignant potentials ranged from 0% to 65% of neoplastic cells with mostly weak to moderate staining intensity. Instead, cyclin D1 expression was <5% in all LMSs. The ratio of MCM2 positivity exhibited a similar wide range (<1%-80%) in LMs, LBNs, and smooth muscle tumors of uncertain malignant potentials but interestingly, 92% (12/13) of LMSs were diffusely and strongly positive for MCM2 (>80% cell positivity). Overall, for diagnosis of LMS, the sensitivity for diffuse intense MCM2 staining was higher (92%) compared with diffuse staining for p16 (77%); however, specificity of MCM2 and p16 was comparable (94% and 97%, respectively). Herein, we describe the immunohistochemical profile of 2 new proliferation markers, cyclin D1 and MCM2 in uterine smooth muscle tumors. A combination of diffuse strong MCM2 and p16 reactivity with increased Ki67 index can reliably distinguish LMSs from benign histologic mimics.

Imaging features of pure and mixed forms of mucinous breast carcinoma with histopathological correlation.

METHODS:: A cross-sectional study identified cases of mucinous breast carcinoma from pathology records (2004-2012). Two radiologists classified imaging features by consensus and two pathologists classified cases into pure or mixed subtypes. Bi-variable analyses were performed using relevant statistical tests. RESULTS:: We identified 80 lesions in 77 female patients (median age 65 years, range 29-88): 58 lesions on mammograhy, 72 on ultrasound, and 25 on MRI. Statistically significant findings (p < 0.05) are as follows. On mammography, tumour margins tended to be indistinct (12, 48%) and spiculated (11, 44%) for pure and mixed lesions, respectively. Pure mucinous masses were less microcalcified (23, 77%) and mixed masses equally so. On ultrasound, pure tumours tended towards an irregular or oval shape (44, 42%) with mixed tumours having an irregular shape (78%). More pure tumours (53%) had posterior acoustic enhancement than mixed lesions (33%), and all pure tumours lacked posterior acoustic shadowing. Pure lesions had a heterogeneous echo pattern more than mixed tumours (78% vs 39%). On MRI, pure tumours tended towards a persistent kinetic curve (42%) whereas mixed tumours predominantly had a washout pattern (75%). Most pure tumours were T2 hyperintense (83%) whereas mixed lesions were T2 isointense or hyperintense (61%, 23%), respectively. CONCLUSION:: An analysis of imaging features can help to infer underlying histology of pure and mixed forms of mucinous breast carcinoma. ADVANCES IN KNOWLEDGE:: Pure mucinous carcinomas present less suspicious imaging features than mixed mucinous carcinomas and could be mistaken for non malignant lesions. An imaging analysis of mucinous breast carcinoma can help infer their underlying histology.

Pilot study investigating the prognostic significance of thymidine phosphorylase expression in patients with metastatic breast cancer: a single institution retrospective analysis.

BACKGROUND: The thymidine phosphorylase (TP) enzyme is expressed in higher levels in cancer tissue when compared with normal tissue. It is involved in the intratumoral activation of widely prescribed pyrimidine-derived antimetabolites such as 5'-deoxy-5-fluorouridine and capecitabine (Xeloda(®)). The purpose of this study was to determine the clinical correlation between TP expression in tumor tissue and the clinical outcome of capecitabine-based therapy in patients with locally advanced (stage III) or metastatic breast cancer (stage IV). METHODS: The following variables were analyzed as potential determinants of benefit from a capecitabine-based therapy: TP expression, estrogen receptor (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor-2 status, and Ki67 status. This was accomplished by immunohistochemical analysis of paraffin-embedded cancer tissues from 18 patients with breast cancer treated with at least one cycle of capecitabine. Clinical outcome was measured as time to progression. RESULTS: TP staining intensities in both the invasive and in situ components in patients with lobular and ductal carcinomas were reported. Higher levels of TP in the invasive component were expressed in ER-negative tumors when compared with ER-positive tumors (P<0.05). The ER-positive group expressing lower levels of TP had a median time to progression of 13 months compared with the ER-negative group expressing higher levels of TP which had a median time to progression of 7.5 months (P=0.14). CONCLUSION: Patients with ER-positive tumors expressing lower levels of TP exhibit a longer time to progression when compared with patients with ER-negative tumors. Consequently, tumor TP expression does not seem to predict the outcome of capecitabine-based chemotherapy.

The role of immunohistochemistry in the diagnosis of flat urothelial lesions: a study using CK20, CK5/6, P53, Cd138, and Her2/Neu.

Although differentiating reactive urothelial atypia from urothelial carcinoma in situ (CIS) relies primarily on histologic evaluation, confirming the morphologic impression using immunohistochemistry (IHC) has been increasingly used in routine clinical practice. The aims of this study are to confirm the utility of commonly used markers (CK20, P53) and to test the performance of CK5/6, CD138, and Her2/Neu in the diagnosis of CIS. Using a tissue microarray comprising 52 cases of normal/reactive urothelium and 45 cases of CIS, the IHC evaluation of 5 markers was undertaken. Although the individual specificity of CK20, P53, and Her2/Neu was high (94%, 90%, and 93%, respectively), their sensitivity for CIS detection was lower, with the most sensitive marker being HER2/Neu (63%). Whereas 78% of CIS shows positivity of at least 2 of those 3 markers, only 1 case of reactive urothelium shows positivity for 2 of those 3 markers. The discriminatory performance of CK5/6 and CD138 was poor. In conclusion, HER2/Neu can be added to a panel of CK20 and P53 to help differentiate reactive atypia from CIS in difficult cases. Positive staining for at least 2 of the 3 antibodies (CK20, P53, and HER2/Neu) is strongly associated with CIS. However, the histologic findings should be a primary determinant in the diagnosis of flat urothelial lesions, with IHC playing a supportive confirmatory role.