It was hypothesized that four histopathological types or subtypes of breast carcinoma were undifferentiated types characterized by bidirectional differentiation toward both luminal epithelial and myoepithelial cells and had characteristic molecular changes: invasive ductal carcinoma (IDC) with a large central acellular zone, atypical medullary carcinoma (a subgroup in Grade 3 solid-tubular carcinoma), matrix-producing carcinoma, and spindle-cell carcinoma (or carcinoma with spindle-cell metaplasia). In 32 cases of the undifferentiated type and 37 cases of the relatively differentiated types, we immunohistochemically examined the expressions of myoepithelial markers and KIT, epidermal growth factor receptor (EGFR), and c-erbB-2 oncoproteins. Vimentin, S-100, and α α α α-smooth muscle actin were positive in 28 (88%), 22 (69%), and 15 (47%) of the undifferentiated types, but were positive in seven (19%), one (3%), and one (3%) of relatively differentiated types (P < 0.0001). KIT and EGFR overexpressions were detected more frequently in the undifferentiated types (34 and 88%, respectively) than in relatively differentiated types (3 and 3%, respectively) (P < 0.0001, for both). In 11 (85%) of 13 cases with KIT overexpression, EGFR overexpression concurred. c-erbB-2 overexpression was almost equally detected in both the undifferentiated and relatively differentiated types, and did not correlate with KIT or EGFR overexpression. I n recent studies, mammary epithelial stem cells were shown to play roles in proliferation and remodeling of the mammary gland, and are also considered to be the primary targets for tumorigenesis in the adult mammary glands.(1) The stem cells also form the tumor stem-cell population. The mammary epithelial stem cells are undifferentiated cells and have potential of self-renewal by symmetrical or asymmetrical cell division and bidirectional differentiation to either luminal epithelial cells or myoepithelial cells through the stage of transit amplifying cells (or progenitor cells).(1) A stem cell is likely to be a small, undifferentiated cell that does not express markers of full differentiated myoepithelial and luminal epithelial cells, although the combinations of certain markers for both lineages have been suggested as being characteristics of the stem cells. In a previous study, we reported that the expression of myoepithelial cell markers, for example, vimentin, α-smooth muscle actin, and S-100 protein, were frequent in invasive ductal carcinoma (IDC) of solid-tubular subtype, nuclear grade 3, of the breast.(3) Vimentin, a mesenchymal marker, is also shown to be a molecule expressed by myoepithelial cells.(2) Therefore, it is compatible to consider that these immunophenotype observed in this breast carcinoma type would indicate its bidirectional differentiation toward luminal epithelial and myoepithelial cells.The KIT proto-oncogene encodes a growth factor receptor with tyrosine kinase activity and is involved in the growth and development of mast cells and of premature stromal cell or inter...

No abstract

No abstract

Purpose: The aim of this study was to assess the reliability of Ki-67 expression on core needle biopsy (CNB) and the surgical specimens of invasive breast cancer. We examined the concordance rate of Ki-67 expressions, hormone receptors, and human epidermal growth factor receptor 2 (HER2) status from a CNB with from a surgery in invasive breast cancer. Methods: A retrospective study was conducted on a clinical database of patients who underwent surgery for early breast cancer. Of these, 193 patients who underwent CNB before the surgery were enrolled. A cutoff value of 20% was used for Ki-67-positive criteria. Expression of estrogen receptor (ER), progesterone receptor (PgR), and HER2 were examined and compared with that of Ki-67. To evaluate discordance between the pathologists' earlier assessments, we reexamined Ki-67 expression among the Ki-67 discordant group in a central laboratory. Results: The concordance rate for Ki-67 expression between the two specimen types was 77.7%, which was significantly lower than that for ER, PgR, and HER2 expression (95.9%, 88.1%, and 91.6%, respectively). The concordance rate for reexamined Ki-67 expression among the Ki-67 discordant group improved to 93.8% and was not significantly different from that for the other receptors. Conclusion: The concordance rate for Ki-67 expression between biopsy and surgical specimens was significantly lower than that for ER, PgR, and HER2 expressions, but re-examination of Ki-67 expression in a central laboratory revealed no significant difference among the receptors, suggesting the need for standard pathological assessment of Ki-67 expression for clinical use as a predictive marker of breast cancer.

Purpose: To standardize the methods to measure Ki-67, there is an interest in automating the assessment of Ki-67. Therefore, we reviewed the possibility of introducing an automated analyzer to standardize the Ki-67 evaluation method. Methods: We retrospectively reviewed a clinical database of patients who underwent surgery for early breast cancer at Tokyo-West Tokushukai Hospital. Among them, those who underwent preoperative core needle biopsy (CNB) were enrolled. The concordance rates of estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki-67 by local pathologists were reviewed (valuations made by local pathologists), and nonmatching cases (from August 2008 to October 2011) were reassessed both by central review and using an automated analyzer with virtual slides. The results were compared with the evaluations made by local pathologists, and we reexamined the concordance rate by using central review and the automated analyzer. Results: The concordance rate of Ki-67 evaluations made by local pathologists in the preoperative CNB and surgical specimens was 78.7% in 287 cases pathologically assessed from October 2008 to March 2013. This rate was significantly lower (p < 0.01) than that of ER (95.6%), PgR (88.5%), and HER2 (91.6%). Reassessment of the 37 cases of nonmatching Ki-67 values from 2008 to October 2011 using central review and an automated analyzer resulted in clear improvement in matching of 22 (92.1%) and 24 (93.1%) of 37 cases, respectively. Conclusion: The concordance rate of Ki-67 in preoperative CNB and surgical specimens was lower than that of other biological markers; however, they were nearly equal by reassessment using central review and an automated analyzer.