Paul Pharoah and colleagues evaluate the prognostic significance of immunohistochemical subtype classification in more than 10,000 breast cancer cases with early disease, and examine the influence of a patient's survival time on the prediction of future survival.

The International Society of Urological Pathology 2012 Consensus Conference made recommendations regarding classification, prognostic factors, staging, and immunohistochemical and molecular assessment of adult renal tumors. Issues relating to prognostic factors were coordinated by a workgroup who identified tumor morphotype, sarcomatoid/rhabdoid differentiation, tumor necrosis, grading, and microvascular invasion as potential prognostic parameters. There was consensus that the main morphotypes of renal cell carcinoma (RCC) were of prognostic significance, that subtyping of papillary RCC (types 1 and 2) provided additional prognostic information, and that clear cell tubulopapillary RCC was associated with a more favorable outcome. For tumors showing sarcomatoid or rhabdoid differentiation, there was consensus that a minimum proportion of tumor was not required for diagnostic purposes. It was also agreed upon that the underlying subtype of carcinoma should be reported. For sarcomatoid carcinoma, it was further agreed upon that if the underlying carcinoma subtype was absent the tumor should be classified as a grade 4 unclassified carcinoma with a sarcomatoid component. Tumor necrosis was considered to have prognostic significance, with assessment based on macroscopic and microscopic examination of the tumor. It was recommended that for clear cell RCC the amount of necrosis should be quantified. There was consensus that nucleolar prominence defined grades 1 to 3 of clear cell and papillary RCCs, whereas extreme nuclear pleomorphism or sarcomatoid and/or rhabdoid differentiation defined grade 4 tumors. It was agreed upon that chromophobe RCC should not be graded. There was consensus that microvascular invasion should not be included as a staging criterion for RCC.

Previous studies have shown that BRCA1-related breast cancers are often high-grade tumors that do not express estrogen receptors, HER2, p27Kip1 , or cyclin D1, but do express p53 and cyclin E. In addition, the expression of cytokeratin 5/6 (CK5/6), indicating a basal epithelial phenotype, is frequent in BRCA1-related breast cancer. Here, in a series of 247 breast cancers, we demonstrate that CK5/6 expression was associated with nearly all of the features of BRCA1-related breast cancer and was also associated with a poor prognosis. In a parsimonious multivariable proportional hazards model, protein levels of cyclin E, p27Kip1 , p53, and the presence of glomeruloid microvascular proliferation all independently predicted outcome after breast cancer. In this model, only cyclin E and p27Kip1 levels were independent predictors in lymph node-negative cancers, whereas glomeruloid microvascular proliferation and tumor size independently predicted outcome in node-positive disease. The molecular determinants of the basal epithelial phenotype encapsulate many of the key features of breast cancers occurring in germ-line BRCA1 mutation carriers and have independent prognostic value. Basal breast cancer deserves recognition as an important subtype of breast cancer.

Background: Basal-like breast cancer has been extensively characterized on the basis of gene expression profiles, but it is becoming increasingly common for these tumors to be defined on the basis of immunohistochemical (IHC) staining patterns, particularly in retrospective studies where material for expression profiling may not be available. The IHC pattern that best defines basal-like tumors is under investigation and various combinations of ER, PR, HER2-, CK5/6+ and EGFR+ have been tested.

Background: The prognostic significance of germline mutations in BRCA1 and BRCA2 in women with breast cancer remains unclear. A combined analysis was performed to address this uncertainty.

Background:Predict (www.predict.nhs.uk) is an online, breast cancer prognostication and treatment benefit tool. The aim of this study was to incorporate the prognostic effect of HER2 status in a new version (Predict+), and to compare its performance with the original Predict and Adjuvant!.Methods:The prognostic effect of HER2 status was based on an analysis of data from 10 179 breast cancer patients from 14 studies in the Breast Cancer Association Consortium. The hazard ratio estimates were incorporated into Predict. The validation study was based on 1653 patients with early-stage invasive breast cancer identified from the British Columbia Breast Cancer Outcomes Unit. Predicted overall survival (OS) and breast cancer-specific survival (BCSS) for Predict+, Predict and Adjuvant! were compared with observed outcomes.Results:All three models performed well for both OS and BCSS. Both Predict models provided better BCSS estimates than Adjuvant!. In the subset of patients with HER2-positive tumours, Predict+ performed substantially better than the other two models for both OS and BCSS.Conclusion:Predict+ is the first clinical breast cancer prognostication tool that includes tumour HER2 status. Use of the model might lead to more accurate absolute treatment benefit predictions for individual patients.

A malignant neoplasm localized to the lung is reported in a rather unusual host: a 40-year-old female, nonsmoker, of South-East Asiatic origin. The histology was of nasopharyngeal-like carcinoma character and ultrastructural examination confirmed a diagnosis of nonkeratinizing, poorly differentiated squamous cell carcinoma. The clinicopathologic findings were more suggestive of a primary pulmonary origin than the manifestation of an occult nasopharyngeal primary. The immunological profile was highly suggestive of an Epstein-Barr virus (EBV) associated epithelial neoplasia. This case might widen the spectrum of EBV-associated neoplasia, by inclusion of lower respiratory tract as a target organ.

~p l f 5~"~, a protein tyrosine kinase (PTK) co-localized with integrtns in focal adhesion plaques, is known to transduce signals invoked in the regulation of cell adhesion and motility as well as the anchorage-independent growth of transformed cells. We investigated whether pp I 25F*K could be part of a signalling pathway that contributes to the progression of human prostate carcinoma (PCa). Up-regulation of pp I 25F*K expression, its activation by phosphoryiation on tyrosine and its association with paxillin and p 5 W were preferentially observed in PCa tissues from patients with metastases, whereas normal and hyperplastic prostates and localized PCa tissues showed undetectable or low levels of both FAK mRNA and protein and an absence of pp12SFAK signalling complexes. The increase in expression and activation of pp I 25FAK in metastatic PCa tissues was also corroborated by our findings in human PCa cell lines. Indeed, higher levels of ~p l 2 5~~and FAK mRNA were observed in highly tumorigenic PC-3 cells as was the presence of activated p~1 2 5 "~, as opposed to an inactive form in LNCaP cells, which have a lower tumorigenic ability. In addition, ~~1 2 5~~ formed signalling complexes with both paxillin and p5Wk in PC-3 cells as in metastatic PCa tissues. Together, our results show that an increase in FAK mRNA and protein, as well as pp 125FM activation and association with signalling proteins, correlates with progression and invasion in human PCa tissues and cells.8 1996 Wiley-Liss, Inc.The processes of tumour formation, invasion and metastasis represent complex genetic and epigenetic events that lead to cell transformation, with subsequent changes in adhesive properties that allow the transformed cells to migrate, gain access to the circulation and form metastatic colonies (Liottaet al., 1991). It is likely that some changes in adhesion occur at focal adhesion plaques which are cell/extracellular matrix (ECM) contact points containing integrin receptors, cytoskeletal components and intracellular signalling proteins such as focal adhesion kinase ( p~1 2 5~"~) , a non-receptor protein tyrosine kinase (PTK) (Clark and Brugge, 1995; Schaller et al., 1992). Evidence from several laboratories has shown that cell adhesion to the ECM through the integrin receptors leads to an increase in the tyrosine phosphorylation of pp12FAK and a subsequent stimulation of its activity (Juliano and Haskill, 1993). Phosphorylation of ~~1 2 . 5~~ is also increased in Rous sarcoma virus-transformed cells, as a result of the expression of ~p 6 0 ' ' -~~~ oncogene product, which is also a PTK (Guan and Shalloway, 1992). These changes lead to the disassembly of actin filaments and focal adhesions and, consequently, to a decrease in cell adhesion and an increase in anchorageindependent growth.As part of the integrin signalling pathway, ~~1 2 5~"~ has also been shown to be associated with various intracellular proteins in fibroblasts and transformed cells . Among them, paxillin, a cytoskeletal phosphotyrosine (pY)-containing protein invol...