Elucidating the prognostic significance of KRAS, NRAS, BRAF and PIK3CA mutations in Chinese patients with metastatic colorectal cancer.

AIM: The prognostic significance of KRAS, NRAS, PIK3CA and BRAF mutations was evaluated in Chinese patients with metastatic colorectal cancer (CRC). METHOD: Tumor samples from 183 patients were retrospectively tested for KRAS, NRAS, PIK3CA and BRAF mutations. Multivariate analysis was performed to determine the relationship between mutational status, drug response and survival. RESULT: Over 70% of patients received two or more lines of chemotherapy, 50% had cetuximab and 18% had bevacizumab. The prevalence of KRAS, NRAS, BRAF and PIK3CA mutations was 45, 3.2, 5 and 20%, respectively. For the entire cohort, the median overall survival was 24 months (95% confidence interval [CI] = 20.4-26.4 months). Of the genes tested, only KRAS mutation was an independent prognostic factor with a multivariate hazard ratio of 1.5 (95% CI = 1.05-2.16, P = 0.03). In the subgroup of patients who received cetuximab-based therapy in the first-line setting, KRAS mutation was associated with a lack of response to chemotherapy (28% vs 66%, chi-square, P = 0.01). Patients with KRAS mutant tumors (or KRAS wild-type tumors that harbored BRAF and/or PIK3CA mutations) tended to have lower response rates to chemotherapy and/or cetuximab (P = not significant). The number of NRAS mutant cases was too small to allow any statistical analysis. CONCLUSION: The prevalence of KRAS, NRAS, BRAF and PIK3CA mutations in this cohort is consistent with reports from non-Asian populations, and KRAS mutation has both prognostic and predictive significance in Chinese patients with metastatic CRC.

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.

p63 is useful in the diagnosis of mammary metaplastic carcinomas.

AIMS: p63 has been recently reported to be expressed in sarcomatoid/metaplastic carcinoma of the breast, in addition to its role as a myoepithelial marker. A large series of 34 metaplastic carcinomas, including cases with pure epithelial component (squamous cell and adenosquamous carcinomas), biphasic tumours with carcinomatous and sarcomatoid components and monophasic tumours with only spindle cell component, were evaluated for p63 expression with respect to the different cellular components. METHODS: All of the metaplastic carcinomas were assessed for p63 and conventional epithelial and mesenchymal markers of AE1/3, CAM5.2 and vimentin by immunohistochemistry. RESULTS: All of the different categories of metaplastic carcinomas showed similar clinico-pathological features (patient age, tumour size, nuclear grade, mitotic activity, lymph node status and hormonal receptor status). For metaplastic carcinoma with epithelial component only, p63 was only expressed in the squamous cell component, but not the adenocarcinoma component. Eight of the 10 tumours were positive for p63. For the tumours with sarcomatoid component, either singly or together with carcinomatous component, p63 was positive in 14 of 24 cases. Pure sarcomas and carcinomas were all negative for p63 staining by immunohistochemistry, thus rendering p63 staining highly specific for diagnosing metaplastic carcinoma. CONCLUSIONS: Using p63 for diagnosis of metaplastic carcinoma gives a sensitivity of 65%, a specificity of 96%, a positive predictive value of 96%, and a negative predictive value of 66% and an accuracy of 78%. p63 may be used as an adjunct marker in the diagnosis of metaplastic carcinoma.