BackgroundEstablished measurements of proliferation in breast cancer are Ki67 and mitotic-activity-index (MAI), with problems in reproducibility and prognostic accuracy. Phosphohistone H3 (PHH3), a relatively novel IHC marker is specific for mitosis with good reproducibility. We hypothesized that PHH3 would be more reproducible and better represent proliferation than Ki67.ResultsPHH3 identified easily-missed mitosis by MAI, as demonstrated by upgrading M grade at diagnosis (n = 29/218, evenly distributed). PHH3 accurately found hot-spots, supported by mitotic count agreement between low-power and 10HPFs (R2 = 0.999; P = 0.001). PHH3 was more reproducible than Ki67, measured by five-rater inter-class correlation coefficient (0.904 > 0.712; P = 0.008). Finally, despite a relatively short follow-up (median 46 months; 7 recurrences) PHH3 was the only variable correlated with disease-free survival (P = 0.043), while all other conventional clinicopathologic variables, including Ki67 (P = 0.356), did not.Materials and MethodsWe compared Ki67 and PHH3 for 218 breast cancer surgical cases diagnosed from 2012 to 2013 at Severance hospital. The most representative invasive breast cancer surgical slides were immunohistochemically stained for Ki67 and PHH3.ConclusionsPoor reproducibility and inadequate representation of proliferation of Ki67 and MAI may be improved by PHH3, allowing better accuracy in breast cancer diagnostics.

Local recurrence of phyllodes tumor (PT) of the breast is an adverse outcome that can result in sarcomatous degeneration. The aim of this study was to investigate the histologic and surgical factors associated with local recurrence. A total of 193 PT cases were studied: 145 (75.1 %) benign cases, 33 (17.1 %) borderline cases, and 15 (7.8 %) malignant cases. Stratifying our analysis according to histologic grade, we investigated the relationship between disease-free survival (DFS) and both histologic and surgical factors, including histologic grade, stromal cellularity, stromal atypia, stromal mitosis, stromal overgrowth, tumor margin, type of surgical procedure (local excision, wide excision, and mastectomy), surgical margin status, and radiation therapy. In the case of benign PT, all patients with local recurrences (3.4 %) had been treated with local excision, and all recurrent tumors were also benign. The local recurrence rate for locally excised benign PTs was not associated with surgical margin status or radiation therapy. In the case of borderline PT, local excision was associated with an increased local recurrence rate (P = 0.046). In malignant PT, small tumor size (≤4.0 cm) was associated with an increased local recurrence rate (P = 0.041). Univariate analyses indicated that surgical procedure (mastectomy < local excision < wide excision; P < 0.001) was significantly associated with shorter DFS in borderline PT. A positive surgical resection margin (P < 0.001) was associated with DFS in malignant PT. The factors associated with local recurrence differed with the histologic grade of PT, as did the features of local recurrence itself. In particular, benign PT had very low rate of local recurrence regardless of surgical margin status or radiation therapy, even when treated with local excision. In the case of benign PT, no recurrent tumors had worse histologic grades than the initial tumors.

Hypothalamic neurons including proopiomelanocortin (POMC)-producing neurons regulate body weights. The non-motile primary cilium is a critical sensory organelle on the cell surface. An association between ciliary defects and obesity has been suggested, but the underlying mechanisms are not fully understood. Here we show that inhibition of ciliogenesis in POMC-expressing developing hypothalamic neurons, by depleting ciliogenic genes IFT88 and KIF3A, leads to adulthood obesity in mice. In contrast, adult-onset ciliary dysgenesis in POMC neurons causes no significant change in adiposity. In developing POMC neurons, abnormal cilia formation disrupts axonal projections through impaired lysosomal protein degradation. Notably, maternal nutrition and postnatal leptin surge have a profound impact on ciliogenesis in the hypothalamus of neonatal mice; through these effects they critically modulate the organization of hypothalamic feeding circuits. Our findings reveal a mechanism of early life programming of adult adiposity, which is mediated by primary cilia in developing hypothalamic neurons.

Summary: Deep inferior epigastric artery perforator (DIEP) flap surgery is one of the most common techniques for breast reconstruction using abdominal tissue. Although the DIEP flap reduces donor-site morbidity when compared with the conventional free transverse rectus abdominis musculocutaneous flap, violation of the anterior rectus sheath, rectus muscle, and motor nerves cannot be avoided. To further minimize tissue damage in the donor site, the use of a surgical robotic system for DIEP flap harvest with a totally extraperitoneal approach has been suggested. This totally extraperitoneal approach has a long learning curve because of the narrow preperitoneal space and the difficulty of converting a potential space to an actual space. Thus, the authors suggest a single-port robotic system optimized for narrow surgical spaces as a feasible option for DIEP flap harvest by a totally extraperitoneal approach, which has a shorter learning curve.

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Despite the emerging literature supporting the beneficial role of vitamin D on various health outcomes including carcinogenesis, current evidence on the association between vitamin D and breast cancer is still largely inconsistent. Furthermore, this relationship is particularly under explored among Asian population. We conducted a large case-control study with Korean women. We obtained and compared serum 25-hydroxyvitamin D (25(OH)D) between breast cancer patients (N = 3634) and general population (N = 17,133). Moreover, we further examined the association between serum 25(OH)D and breast cancer risk stratified by menopausal status and hormone receptor (HR) status of the tumor. Adjusted odds ratio (OR) for breast cancer comparing women with deficient level of serum 25(OH)D to women with sufficient level of serum 25(OH)D was 1.27 [95 % confidence interval (CI) 1.15-1.39]. This association did not significantly vary by menopausal status [pre-menopause: 1.26 (95 % CI 1.09-1.45) vs. post-menopause: 1.25 (95 % CI 1.10-1.41)]. When stratified by HR status, the inverse association remained significant in both positive and negative statuses. However, this association was more pronounced in HR-negative breast cancer, particularly with triple-negative breast cancer patients (1.45, 95 % CI 1.15-1.82). Given the growing burden of breast cancer in Asia and dearth of studies examining the association between vitamin D and breast cancer risk in Asian women thus far, this study provides a meaningful evidence for potential preventive effect of vitamin D on breast cancer for this particular population.