Nerve growth factor receptor (NGFR): a potential marker for specific molecular subtypes of breast cancer.

AIMS: Nerve growth factor receptor (NGFR) is a transmembrane receptor for the neurotrophin family. It acts either as tumour suppressor or oncogene depending on cellular context. Its role in breast cancers remained conflicting, possibly due to the heterogeneity of breast cancer subtypes. METHODS: In this study, we have analysed NGFR expression in 602 cases of breast cancers by immunohistochemistry. Its expression was correlated with biomarker expression and different breast cancer subtypes. RESULTS: NGFR expression was found to be positively correlated with basal markers, including Ki67, Cytokeratin (CK5/6), CK14, p63, c-kit and Epidermal growth factor receptor (EGFR) , but negatively with hormonal receptors. Among different molecular subtypes, it was negatively associated with luminal A, but positively with luminal B, and basal-like breast cancer BLBC subtypes. When comparing NGFR with other basal markers in BLBC, though less sensitive, its specificity was comparable to or better than other basal markers. For luminal B cancers, NGFR showed a high specificity which was also comparable to or better than the defining markers (estrogen receptor (ER), progesterone receptor (PR), Human epidermal growth receptor 2 (HER2) and Ki-67) for the subtype. CONCLUSIONS: Overall, these findings suggested that NGFR expression could be indicative for the BLBCs or luminal B subtypes. It may represent a potential adjunct marker for these two subtypes.

Keratin expression in breast cancers.

Cytokeratin (CK) immunohistochemistry can play an important role in breast carcinoma evaluation. We evaluated the expression of a panel of commonly used CKs in a large cohort of breast cancers and assessed its correlation with other biomarkers and breast cancer subtypes. Expression of CK7, CK8, CK18 and CK19 was observed in more than 90 % of all breast carcinomas in this study, confirming their efficacy in immunohistochemical identification of breast cancer. A combination of CK8 and CK7 gave the highest sensitivity for detection of a minute number of breast cancer cells. Expression of other CKs, including CK5/6, CK14 and CK20, correlated positively with high tumour grade. The expression of CK5/6 and CK14 in a significant number of high-grade tumours raised concern regarding the use of absence of their expression to identify breast carcinoma. For identification of the basal subtype, CK5/6 gave a higher detection rate than CK14. CK20 expression was found more frequently than reported in previous studies, might constitute an indicator of poor prognosis and may be associated with the molecular apocrine subtype. This study highlights the diagnostic and prognostic relevance of the unique CK expression patterns in breast cancer.

Involvement of α- and ß-catenins and E-cadherin in the development of mammary phyllodes tumours.

AIMS: Phyllodes tumours (PT) are rare but clinically important fibroepithelial tumours of the breast. ß-Catenin, a key component in Wnt signalling, has been shown to be important in the development of PT. It also functions as a component of the cadherin complex, which may therefore be implicated in PT pathogenesis. By assessing stromal α-catenin, ß-catenin and E-cadherin expression in 158 PT cases using immunohistochemistry and examining associations with clinicopathological features, we aimed to determine the role of these proteins in PT pathogenesis. METHODS AND RESULTS: Cytoplasmic ß-catenin correlated with α-catenin expression. A significantly higher expression of both markers was observed in borderline than in benign PT (P = 0.003 and <0.001, respectively), but a lower level was found in malignant PT. Cytoplasmic E-cadherin expression was significantly higher in borderline and malignant than in benign PT (P = 0.001 and 0.012, respectively), but was not correlated with other markers. Both E-cadherin and α-catenin showed stronger correlations with histological parameters than ß-catenin. α-Catenin showed a significant correlation with recurrence (P = 0.005 and 0.016, respectively). CONCLUSION: α- and ß-catenins may be important in the early stages of PT development, while E-cadherin may be required for malignant development. The correlation of α-catenin expression with tumour recurrence may be relevant in predicting PT behaviour.

αB-crystallin is a useful marker for triple negative and basal breast cancers.

AIMS: Basal-like breast cancers (BLBCs), a breast cancer subtype with triple-negative status, pose significant problems in clinical management because of their aggressive behaviour. Recently, an association between αΒ-crystallin expression and BLBCs has been suggested, and we therefore investigated whether αΒ-crystallin could be a putative marker allowing BLBCs to be identified more accurately. METHODS AND RESULTS: We evaluated the expression of αB-crystallin and other biomarkers in 395 cases of breast carcinoma by immunohistochemistry, analysed the correlation of their expression with different breast cancer subtypes, and compared their sensitivity as well as specificity in identifying BLBCs. αΒ-crystallin expression was found to be correlated positively with basal markers and histological subtypes associated with BLBCs. A significant positive correlation of αΒ-crystallin expression was also found with triple-negative breast cancers (TNBC) (C = 0.409, P < 0.001) and BLBCs (C = 0.393, P < 0.001). Comparing αΒ-crystallin with other basal markers, only αΒ-crystallin demonstrated both high sensitivity (48.6%) and specificity (93.8%) as a TNBC marker. All other markers showed either a lower sensitivity of <40% or a lower specificity of <90%. αΒ-crystallin also demonstrated a high specificity (92.9%) and an even higher sensitivity (56.5%) for BLBCs. CONCLUSIONS: The findings indicated that αB-crystallin was a highly sensitive and specific marker for TNBCs and BLBCs.

Phyllodes tumours of the breast - differentiating features in core needle biopsy.

AIMS: To investigate the usefulness of histological features in the differentiation of fibroepithelial lesions of the breast (phyllodes tumours and fibroadenomas) in core needle biopsies. METHODS AND RESULTS: Forty-nine and 69 excision-proven core biopsies of phyllodes tumours and fibroadenomas, respectively, were evaluated histologically for stromal cellular changes (overall stromal cellularity, variability in stromal cellularity, stromal cell pleomorphism, and mitotic count) and stromal architectural changes (stromal overgrowth, fragmentation of the cores, and fat in stroma). In core needle biopsies of phyllodes tumours, overall stromal cellularity, stromal cell pleomorphism and mitotic count showed good correlation with excisions. In phyllodes tumours, core needle biopsy diagnosis showed increased certainty with increasing degree of malignancy. Core biopsies of phyllodes tumours showed more consistent stromal cellular changes (overall stromal cellularity, variability in stromal cellularity, stromal pleomorphism, and mitotic count) than those of fibroadenomas. These parameters were also useful for differentiation between benign and malignant fibroepithelial lesions. For grading phyllodes tumours, stromal cell pleomorphism and mitotic activity were found to be helpful. CONCLUSIONS: In the core biopsy assessment of phyllodes tumours, evaluation of selected histological parameters, particularly those pertaining to stromal cellular changes, is helpful.

Granulomatous mastitis: the histological differentials.

BACKGROUND: The management of granulomatous mastitis depends on the causative factor, and accurate diagnosis in distinguishing between idiopathic granulomatous mastitis (IGM) and tuberculous mastitis (TBM) is indispensable. This is particularly problematic in the cases of granulomatous mastitis in which the microbiological studies are negative. In this study, in a large cohort, the histological features for IGM and TBM were compared. METHODS: The histopathology files from the two participating hospitals were searched for cases of granulomatous inflammation of the breast over an 8-year period. The parameters assessed included age of patient, lesional size, systemic and local symptoms, and histological findings of inflammatory cells, granulomas, necrosis, multinucleated giant cells, fibrosis and calcifications. RESULTS: 29 cases of IGM and 33 cases of TBM were included in this study. A significant difference was seen between the two groups with regard to patient age (t=2.52, p<0.05) and lesional size (t=-5.56, p<0.01). TBM occurred in a significantly younger population, and demonstrated larger lesional sizes than IGM. There was no difference between the number of cases showing mass, local and systemic symptoms. Comparing the different histological features, the TBM group showed significantly more fibrosis, eosinophils and necrosis, whereas the IGM group showed significantly more plasma cells. Taking all the cases together as one group to evaluate the relationship between the histological parameters, there was significant positive correlation between eosinophils and fibrosis (r(s)=0.39, p<0.01), and negative correlation between vague and well-formed granulomas (r(s)=-0.38, p<0.01). CONCLUSION: TBM was more likely to occur in younger patients, with a larger clinical mass at presentation. Histologically, TBM tends to show more eosinophils and necrosis, and IGM is associated with more plasma cells. The characteristics of the granulomas and giant cells were not distinguishing features.

Correlation of biomarkers in head and neck squamous cell carcinoma.

OBJECTIVE: To evaluate the relationship of functional magnetic resonance imaging (MRI) parameters, including choline/creatine ratio (Cho/Cr) and apparent diffusion coefficient (ADC) with protein expression of 10 common tumor and prognostic markers in head and neck squamous cell carcinoma. STUDY DESIGN: Cross-sectional study. SETTING: University hospital. SUBJECTS AND METHODS: The Cho/Cr and ADC obtained from 74 patients with head and neck squamous cell carcinoma were correlated with the expression level of the 10 protein markers as determined by immunohistochemistry. RESULTS: Cho/Cr showed significant positive correlations with cyclooxygenase 2 in primary tumors (r = 0.714), and epidermal growth factor receptor in metastatic cervical lymph nodes (r = 0.522). ADC showed significant (r = -0.591) negative correlation with human epidermal growth factor receptor 2 in metastatic cervical lymph nodes. CONCLUSION: There are relationships between protein and functional MRI markers. Future research in this direction may improve our understanding of the cancer micro-environment.