Low Mitotic Activity Research Articles

A rare case of transitional meningioma.

A rare case of transitional meningioma.

Mid-gut ACTH-secreting neuroendocrine tumor unmasked with (18)F-dihydroxyphenylalanine-positron emission tomography.

SummaryEctopic ACTH Cushing's syndrome (EAS) is often caused by neuroendocrine tumors (NETs) of lungs, pancreas, thymus, and other less frequent locations. Localizing the source of ACTH can be challenging. A 64-year-old man presented with rapidly progressing fatigue, muscular weakness, and dyspnea. He was in poor condition and showed facial redness, proximal amyotrophy, and bruises. Laboratory disclosed hypokalemia, metabolic alkalosis, and markedly elevated ACTH and cortisol levels. Pituitary was normal on magnetic resonance imaging (MRI), and bilateral inferior petrosal sinus blood sampling with corticotropin-releasing hormone stimulation showed no significant central-to-periphery gradient of ACTH. Head and neck, thoracic and abdominal computerized tomography (CT), MRI, somatostatin receptor scintigraphy (SSRS), and 18F-deoxyglucose-positron emission tomography (FDG-PET) failed to identify the primary tumor. 18F-dihydroxyphenylalanine (F-DOPA)-PET/CT unveiled a 20-mm nodule in the jejunum and a metastatic lymph node. Segmental jejunum resection showed two adjacent NETs, measuring 2.0 and 0.5 cm with a peritoneal metastasis. The largest tumor expressed ACTH in 30% of cells. Following surgery, after a transient adrenal insufficiency, ACTH and cortisol levels returned to normal values and remain normal over a follow-up of 26 months. Small mid-gut NETs are difficult to localize on CT or MRI, and require metabolic imaging. Owing to low mitotic activity, NETs are generally poor candidates for FDG-PET, whereas SSRS shows poor sensitivity in EAS due to intrinsically low tumor concentration of type-2 somatostatin receptors (SST2) or to receptor down regulation by excess cortisol. However, F-DOPA-PET, which is related to amine precursor uptake by NETs, has been reported to have high positive predictive value for occult EAS despite low sensitivity, and constitutes a useful alternative to more conventional methods of tumor localization.Learning points Uncontrolled high cortisol levels in EAS can be lethal if untreated.Surgical excision is the keystone of NETs treatment, thus tumor localization is crucial.Most cases of EAS are caused by NETs, which are located mainly in the lungs. However, small gut NETs are elusive to conventional imaging and require metabolic imaging for detection.FDG-PET, based on tumor high metabolic rate, may not detect NETs that have low mitotic activity. SSRS may also fail, due to absent or low concentration of SST2, which may be down regulated by excess cortisol.F-DOPA-PET, based on amine-precursor uptake, can be a useful method to localize the occult source of ACTH in EAS when other methods have failed.

Checkpoint kinase1 (CHK1) is an important biomarker in breast cancer having a role in chemotherapy response.

Background:Checkpoint kinase1 (CHK1), which is a key component of DNA-damage-activated checkpoint signalling response, may have a role in breast cancer (BC) pathogenesis and influence response to chemotherapy. This study investigated the clinicopathological significance of phosphorylated CHK1 (pCHK1) protein in BC.Method:pCHK1 protein expression was assessed using immunohistochemistry in a large, well-characterized annotated series of early-stage primary operable invasive BC prepared as tissue microarray (n=1200).Result:pCHK1 showed nuclear and/or cytoplasmic expression. Tumours with nuclear expression showed positive associations with favourable prognostic features such as lower grade, lower mitotic activity, expression of hormone receptor and lack of expression of KI67 and PI3K (P<0.001). On the other hand, cytoplasmic expression was associated with features of poor prognosis such as higher grade, triple-negative phenotype and expression of KI67, p53, AKT and PI3K. pCHK1 expression showed an association with DNA damage response (ATM, RAD51, BRCA1, KU70/KU80, DNA-PKCα and BARD1) and sumoylation (UBC9 and PIASγ) biomarkers. Subcellular localisation of pCHK1 was associated with the expression of the nuclear transport protein KPNA2. Positive nuclear expression predicted better survival outcome in patients who did not receive chemotherapy in the whole series and in ER-positive tumours. In ER-negative and triple-negative subgroups, nuclear pCHK1 predicted shorter survival in patients who received cyclophosphamide, methotrexate and 5-florouracil chemotherapy.Conclusions:Our data suggest that pCHK1 may have prognostic and predictive significance in BC. Subcellular localisation of pCHK1 protein is related to its function.

Autophagy and ubiquitination in cardiovascular diseases.

A main function of the heart is to pump blood to the tissues and organs of the body. Although formed by different types of cells, the cardiomyocytes are the ones responsible for the coordinated and synchronized heart contraction. Given their low mitotic activity, cardiomyocytes largely depend on protein degradation mechanisms to maintain proteostasis and energetic balance. Autophagy, one of the main pathways whereby cells eliminate damaged, nonfunctional, or obsolete proteins, and organelles, is vital to ensure cell function, including in cardiomyocytes, both in rest and stress conditions. However, the impact of autophagy activation in the heart, being either protective or harmful, is not consensual and likely depends upon the severity of the stimuli and consequently the autophagy players involved. One of the signals that direct proteins for autophagy degradation, namely in the context of heart disorders, is ubiquitin. Indeed, the attachment of ubiquitin moieties to a target substrate and further recognition by autophagy adaptors constitute a main regulatory pathway that directs proteins to the lysosome. Therefore, a better understanding of the mechanisms and signals that regulate the autophagy process in the heart, including substrates targeting, is of utmost importance to design new approaches directed to this degradation pathway. We have previously shown that ubiquitination of the gap junction (GJ) protein Connexin43 (Cx43) triggers its degradation by autophagy through a process that requires the ubiquitin adaptors epidermal growth factor receptor substrate 15 (Eps15) and p62. This is particularly relevant in the heart because GJs, that form intercellular channels, are responsible for the rapid and efficient anisotropic propagation of the electrical impulse through the cardiomyocytes, essential for synchronized contraction of the cardiac muscle. In this review, we present recent studies devoted to the involvement of autophagy in heart homeostasis, with a particular focus on ubiquitin and GJs.

Urachal leiomyoma: a case report

Leiomyoma of the urachus is a rare entity and only a few cases have been reported in the literature. The urachus is an embryonic remnant originating from the involution of the allantois and the ventral cloaca. It connects the allantois and the anterior part of the urinary bladder dome. When it persists after birth, varying pathological conditions can arise. We report a case of urachal leiomyoma in a 35-year-old man who presented with 2 day history of lower abdominal pain. A palpable mass was found on physical examination. CT scan of abdomen and pelvis revealed a heterogeneous necrotic soft tissue mass arising from the roof of the urinary bladder and highly suspicious for an adenocarcinoma arising from an urachal remnant. Laparoscopy was performed and the umbilicus, urachus and part of the bladder were removed. At the junction of the urachus and bladder dome a nodular tumour with a whorling pattern was seen. Microscopically, the tumour was composed of haphazardly arranged fascicles of smooth muscle cells in a nodular pattern with mild to moderate degenerate type cellular atypia with central ischaemic necrosis and low mitotic activity.

Przebieg mitozy w korzeniach siewek pszenicy pod wpływem rubidu [Course of mitosis in root seedlings of Triticum aestivum L. under the influence of rubidium

The depresion of mitosis as a result of rubidium action illustrated by the lower frequency of mitosis was found in an investigation made on roots of wheat seedlings grown on a nutrient medium which the total amount of potassium or a half of it was replaced by rubidium. The lower mitotic activity was caused by limited number of nuclei beginning prophase and by a prolonged duration of metaphase.

Sert Damağın Hiyalinize Berrak Hücreli Adenokarsinomu

Hyalinizing clear cell adenocarcinoma is a rare tumor originating from minor salivary glands. 48 years old male patient presented with painless swelling on the hard palate. Computerized tomography and magnetic resonance imagination of the maxilla revealed 3 cm by 3 cm sized, heterogenous gadolinium enhancing mass which was originating from the incisive theet gingiva and extending to the bilateral maxillar arch intraorally and to the palatin bone in the nasal cavity. Incisional biopsy report of the mass was hyalinizing adenocarcinoma of the hard palate. In the light of the biopsy result and radiologic examination wide surgical resection and bilateral supraomohyoid neck dissection was performed. Due to low mitotic activity and nuclear pleomorphism it is defined as low grade tumor according to classic adenocarcinoma leading to better prognosis if treated promptly. Given the rarity and lack of reported series, diagnosis and tretament of this tumor was discussed in the light of the literature.

Assessment of Estrogen receptor Expression in Carcinoma Breast cases presenting to a tertiary care hospital in Andhra Pradesh

Breast carcinoma is the most common malignant tumor and the leading cause of death, in women, worldwide. It accounts for 15 % of all cancer deaths. Various protocols are in use for the assessment of prognosis, and also to assist in planningfurther management of these cases. Of various parameters, expression of Estrogen receptors (ER) is significant. The literature includes several studies showing association between the presence of estrogen receptors apart from other indicators of good prognosis like small tumor size, low histological grade, low nuclear grade and low mitotic activity. It is also a powerful predictive factor for the likelihood of benefit from adjuvant hormonal therapy including aromatase inhibitors (Anastrozole, letrozole) and Tamoxifen, an oral selective estrogen receptor modulator. All cases of Carcinoma breast presenting to S.V.R.R.G.G. Hospital, are evaluated for Estrogen Receptor status using immunochemistry, indirectly assessing the prognosis of individuals presenting to the Hospital and in turn the prognosis of the disease in the region.

Pituitary gene expression differs in D-galactose-induced cell senescence and steroid-induced prolactinomas.

In general, pituitary tumors are benign with low mitotic activity. Premature senescence has been considered to be a significant mechanism underlying this uniquely benign pituitary tumor. The present study aims to compare the expression of the associated proteins involved in premature senescence pathways among normal, aging and pituitary adenoma cells. We successfully induced the aging pituitary using continuous D‑galactose (D‑gal) injection as well as a prolactin‑secreting pituitary tumor via diethylstilbestrol implants. Compared with normal pituitary cells, the aging pituitary tissues revealed increased expression of IL‑6, C/EBPβ, p53, p21 and p16 and decreased expression of pituitary tumor transforming gene. In contrast, the expression of IL‑6, p21 and p16 was decreased in pituitary tumor cells compared with normal pituitary tissues. Taken together, multiple pathways including IL‑6/C/EBPβ, p53/p21 and p16 were activated in aging pituitary cells in response to D‑gal treatment. However, all these pathways were immune to pituitary tumors treated by chronic estrogen. The findings and the involvement of cytokines in a highly prevalent natural disease model (pituitary adenomas) indicate a potential use of this pathway as a target for effective therapy for tumor silencing and prevention of adenoma progression towards malignancy.

Abstract 246: Mammary cancer preventive activity of an extract of withania somnifera roots

Abstract Mammary cancer preventive activity of an alcoholic extract of Withania somnifera (WS) roots was examined in female ErbB2+/- (MMTV/Neu) mice. The WS root extract was mixed with feed at a concentration of 750 mg/kg of diet. Mice treated with the root extract developed fewer mammary tumors relative to mice in the untreated group; after 310 days, mice in the treated group had an average of 1.62 tumors, and mice in the control group had 2.48, a reduction of 33% (p=0.1). Representative samples of the mammary tumors were examined histologically after staining with hematoxylin and eosin (H&amp;E) and for proliferation (Ki67 and PCNA). For mammary tumors of control mice, sections stained with H&amp;E showed high mitotic activity, whereas in tumors from treated mice, there was low mitotic activity. Labeling indices for Ki67 and PCNA markers in cancers of treated mice were 35% and 30% lower, respectively, than those of the control group. Expression of the cytokine CCL2 was 50% lower in cancers of the treated group. These results indicate that the root extract of WS reduces mammary tumor formation and tumor cell proliferation. Supported by grant U54 CA118948. Citation Format: kamel F. Khazal, Donald Hill, Clinton J. Grubbs. Mammary cancer preventive activity of an extract of withania somnifera roots. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 246. doi:10.1158/1538-7445.AM2014-246

Identification and functional validation of RAD23B as a potential protein in human breast cancer progression.

Identification of protein targets that play a role in breast cancer invasion may help to understand the rapid progression of cancer and may lead to the development of new biomarkers for the disease. In this study, we compared two highly invasive and two poorly invasive breast cancer cell lines using comparative label-free LC-MS profiling in order to identify differentially expressed proteins that may be linked to the invasive phenotype in vitro. Forty-five proteins were found to be upregulated, and 34 proteins, downregulated. UV excision repair protein RAD23 homologue B (RAD23B) was found among the downregulated proteins in highly invasive breast cancer cell lines. In poorly invasive breast cancer cell lines, siRNA-mediated downregulation of RAD23B subsequently led to an increase in invasion and adhesion in vitro. Immunohistochemistry analysis of 164 specimens of invasive breast cancer showed that having a high percentage (>80%) of RAD23B positive nuclei was significantly associated with histopathological grades 1 and 2 breast cancer and with low mitotic activity. In addition, a high staining intensity for RAD23B in the cytoplasm was significantly associated with histopathological grade 3 breast cancer. This study suggests a potential role of RAD23B in breast cancer progression and may further imply a tumor suppressor role of nuclear RAD23B in breast cancer.

Solid Pseudopapillary Neoplasm of the Pancreas: Analysis of Seven Cases

Background: The purpose of this study was to describe as well as compare our surgical treatment experiences of solid pseudopapillary neoplasms (SPN) of the pancreas and to provide a review of the literature. Methods: A retrospective analysis of data from Vilnius University Hospital Santariskiu Klinikos (VUH SK) and of the literature, which was researched using Karger Publishers, Springer Science, BioMed Central, and disserCat databases, was conducted. Results: From 2001 to 2012, seven cases were identified with pathologically confirmed SPN diagnosis. A precise preoperative diagnosis was made by computertomography and magnetic resonance imaging. The median diameter of the tumors was 6.36 cm (range 1.5-12 cm). Surgical treatment was undertaken for all patients. Results of the immunohistochemical analysis confirmed a nuclear accumulation of β-catenin. The Ki-67 level was 1-2% in all of the cases. According to our collected data, all types of histological analysis revealed decent prognostic behavior with low mitotic activity (1-2 mitoses per 50 high power fields). Besides, angioinvasion, perineural invasion, and outside capsule invasion were not detected. Conclusions: There was no correlation between more aggressive types of SPN and tumor size, localization, age, and gender.

Recurrent Müllerian adenofibroma of uterus: a clinicopathologic study of 7 cases

To study the clinicopathologic features and differential diagnosis of recurrent Müllerian adenofibroma (MAF) of the uterus. Clinicopathologic information of 7 cases of recurrent MAF of uterus was retrieved from January 1992 to April 2006 and compared with 12 cases of MAF without recurrence and 14 cases of low-grade Müllerian adenosarcoma (MAS). EnVision immunohistochemistry of estrogen receptor (ER), progesterone receptor (PR), smooth muscle actin (SMA), CD10, Ki-67 and p53 were performed in all cases. All cases of recurrent MAF of the uterus were polypoid, lobulated, and broad based mass arising from the corpus or cervix. Microscopically, the tumor consisted of benign epithelial and mesenchymal components with low mitotic activity ( ≤ 1/10 HPF). The clinical and pathologic features of 3 recurrent tumors were similar to their primary tumors, while 4 cases of recurrent tumor presented with focally higher cellularity and mitotic activity, meeting the diagnostic criteria of adenosarcoma. The stromal expression patterns of ER, PR, SMA and p53 in recurrent MAF were similar to those of clinically benign MAF and low-grade MAS. Negative or focally positive stromal cell expression of CD10 was seen infrequently in recurrent MAF (1/7) and clinically benign MAF (1/12). In contrast, a moderate to strong CD10 staining was frequently seen in MAS (9/14, P < 0.05). The difference of Ki-67-labeling index between MAF and MAS did not reach a statistical significance (P > 0.05). Ki-67-labeling index increased in areas of periglandular stromal cuffing as compared with interglandular areas in all MAS cases, but it was not observed in either recurrent MAF or clinically benign MAF cases. Recurrent MAF may be associated with aggressive behavior. It is difficult to distinguish MAF from low-grade MAS. CD10 and Ki-67 staining pattern in stromal cells may be helpful for the differential diagnosis.

Hormonal control of cell division and elongation along differentiation trajectories in roots

The continuous development of roots is supported by a sustainable system for cell production and growth at the root tip. In the stem cell niche that consists of a quiescent centre and surrounding stem cells, an undifferentiated state and low mitotic activity are preserved by the action of auxin and abscisic acid. Stem cell daughters divide several times in the proximal meristem, where auxin and gibberellin mainly promote cell proliferation. Cells then elongate with the help of gibberellin, and become finally differentiated as a constituent of a cell file in the elongation/differentiation zone. In the model plant Arabidopsis thaliana, the transition zone is located between the proximal meristem and the elongation/differentiation zone, and plays an important role in switching from mitosis to the endoreplication that causes DNA polyploidization. Recent studies have shown that cytokinins are essentially required for this transition by antagonizing auxin signalling and promoting degradation of mitotic regulators. In each root zone, different phytohormones interact with one another and coordinately control cell proliferation, cell elongation, cell differentiation, and endoreplication. Such hormonal networks maintain the elaborate structure of the root tip under various environmental conditions. In this review, we summarize and discuss key issues related to hormonal regulation of root growth, and describe how phytohormones are associated with the control of cell cycle machinery.

Lower mitotic activity in BRCA1/2-associated primary breast cancers occurring after risk-reducing salpingo-oophorectomy

Risk-reducing salpingo-oophorectomy (RRSO) is associated with 50% reduction of BRCA1/2-associated breast cancer (BC) risk, possibly through decreased growth activity. In this pilot study, tumor characteristics and growth rates of BRCA1/2-associated primary BCs (PBCs) detected after RRSO were compared with those of PBCs originating without RRSO. From a cohort of 271 women with BRCA1/2-associated screen detected BC, we selected 20 patients with PBC detected ≥12 months after RRSO (RRSO group). Controls were 36 BRCA1/2 mutation carriers with PBC detected without RRSO (non-RRSO group) matched for age at diagnosis (± 2.5 y) and for BRCA1 or BRCA2 mutation. Pathology samples were revised for histological subtype, tumor differentiation grade, mitotic activity index (MAI), estrogen receptor (ER), progesterone receptor (PR), and HER2 status. Tumor growth rates, expressed as tumor volume doubling times (DT), were calculated from revised magnetic resonance and mammographic images. Median age at PBC diagnosis was 52 y (range 35–67). PBCs after RRSO had lower MAIs (12 vs. 22 mitotic counts/2 mm, P = 0.02), were smaller (11 vs. 17 mm, P = 0.01), and tend to be PR-positive more often than PBCs without RRSO (38% vs. 13%, P = 0.07). Differentiation grade, ER, and HER2 status were not different. Median DT was 124 d (range 89–193) in the RRSO group and 93 days (range 54–253) in the non-RRSO group (P = 0.47). BC occurring after RRSO in BRCA mutation carriers features a lower MAI, suggesting a less aggressive biological phenotype. When confirmed in larger series, this may have consequences for BC screening protocols after RRSO.

2. Bilateral multiple nodules in lung: Epstein barr virus associated smooth muscle lesions

Background Presence of multiple nodules in lung is concerning for metastatic tumour and triggers prompt evaluation. Such scenario in a transplant/immunocomprimsed patient is further complicated since infectious aetiology and secondary malignancy need to be considered. Epstein-Barr Virus (EBV) associated smooth muscle tumours are rare lesions that occur in immuno-comprimsed patients. They are typically well-differentiated with low mitotic activity and little cytological atypia. They are believed to represent consequence of multiple infection events rather than metastasis. Methods We report a 51-year-old patient with a history renal transplant and immunosuppression whose surveillance showed multiple bilateral lung nodules. Transthoracic, CT guided fine needle aspiration smears and core biopsy materials were evaluated using light microscopy, immunohistochemistry and in situ hybridisation for EBV associated RNA. Results The fine needle aspiration smears showed rare, inconclusive stromal pieces. The core biopsy samples displayed spindle cell lesion with smooth-muscle features. There was mild cytological atypia without necrosis or mitotic activity. Immunohisto-chemical stains showed spindle cells were positive for SMA (smooth muscle actin), desmin, and vimentin. S-100 and MNF-116 (cytokeratin stain) were negative. In situ hybridisation for EBER showed nuclear positivity. Conclusions: EBV associated smooth muscle tumours can present as multiple bilateral lung nodules mimicking metastatic tumour. Histologically, they show spindle cell lesion with bland cytological features and low mitotic activity. Supportive ancillary findings by immunohistochemistry and in situ hybridization are as follows: (1) positive for SMA, desmin and vimentin, (2) negative for S-100 and epithelial marker MNF-116, and (3) positive for EBER.

Cardiac rhabdomyosarcoma of the left atrium.

Cardiac rhabdomyosarcoma of the left atrium.

A Multidisciplinary Approach to the Management of Atypical Osseous Epithelioid Hemangioendothelioma

Hemangioendothelioma is a rare vascular tumor of intermediate malignant potential. Though epithelioid hemangioendothelioma (EH) is commonly found in soft tissues, it has been known to be present in skeletal tissues. The authors present a case of a 50-year-old woman diagnosed with EH of the iliac bone and acetabulum, who experienced pathological fracture at presentation. This report describes a multidisciplinary approach to the management that includes initial incisional biopsy, curettage, and bone grafting, followed by Intensity Modulated Radiation Therapy. The patient finally underwent hemipelvic resection with allograft reconstruction after recurrence. Histopathological study revealed osseous EH of low mitotic activity that stained positively for CD31, CD34, vimentin, and Factor VIII. Herein, the authors discuss the imaging characteristics, histopathological aspects, cytogenetic findings, and the radiobiological behavior of osseous EH. After an aggressive multidisciplinary intervention, the patient is able to achieve local control with no evidence of distal metastatic disease.

Identification of novel pathogenic copy number aberrations in multiple myeloma: the Malaysian context

BackgroundMultiple myeloma is an incurable disease. Little is known about the genetic and molecular mechanisms governing the pathogenesis of multiple myeloma. The risk of multiple myeloma predispositions varies among different ethnicities. More than 50% of myeloma cases showed normal karyotypes with conventional cytogenetic analysis due to the low mitotic activity and content of plasma cells in the bone marrow. In the present study, high resolution array comparative genomic hybridization technique was used to identify copy number aberrations in 63 multiple myeloma patients of Malaysia.ResultsCopy number aberrations were identified in 100% of patients analyzed (n = 63). Common chromosomal gains were detected at regions 1q, 2q, 3p, 3q, 4q, 5q, 6q, 8q, 9q, 10q, 11q, 13q, 14q, 15q, 21q and Xq while common chromosomal losses were identified at regions 3q and 14q. There were a total of 25 and 5 genes localized within the regions of copy number gains and losses, respectively (>30% penetrance). The LYST, CLK1, ACSL1 and NFKBIA are genes localized within the copy number aberration regions and they represent novel information that has never been previously described in multiple myeloma patients.ConclusionsIn general, due to the differences in genetic background, dietary and lifestyle practices of Malaysian compared to the Caucasian population, these chromosomal alterations might be unique for Asian MM patients. Genes identified in this study could be potential molecular therapeutic targets for the treatment and management of patients with multiple myeloma.

Abstract P5-05-05: Lower mitotic activity in BRCA1/2-associated primary breast cancers occurring after risk-reducing salpingo-oophorectomy

Abstract Background Bilateral salpingo-oophorectomy reduces breast cancer (BC) risk by about 50% in BRCA1/2 mutation carriers when performed premenopausally. It has been hypothesized that growth activity of BCs originating after risk-reducing salpingo-oophorectomy (RRSO) is lower. We compared tumor characteristics and growth rates of BRCA1/2-associated primary BCs (PBCs) detected after RRSO with those of tumors originating without RRSO. Methods From a cohort of 271 female BRCA1/2-associated patients with screen detected BC, 20 BRCA1/2 mutation carriers with PBC detected ≥12 months after RRSO were selected (RRSO group). Controls were 36 BRCA1/2 mutation carriers with PBC detected without RRSO (non-RRSO group) matched for age at PBC diagnosis (± 2.5 years) and for BRCA1 or BRCA2 mutation (intended matching ratio 1:2). Tumor growth rates, expressed as tumor volume doubling times (DT), were calculated. Pathology samples were revised for histological subtype, tumor differentiation grade, estrogen receptor (ER), progesterone receptor (PR) and HER2 status. Imaging examinations (magnetic resonance imaging (MRI), mammography) before and at BC diagnosis were revised. Results Median age at PBC diagnosis was 52 years (range 35-67). MRI detected more BC than mammography in the RRSO-group as compared to the non-RRSO group (83% vs. 39%, P = 0.02). Tumor size at diagnosis was smaller in the RRSO group (11.0 mm vs. 17.0 mm, P = 0.01). Mitotic activity indexes (MAI) in the RRSO and non-RRSO group were 12 vs. 22 mitotic counts/2 mm2 (P = 0.02). No significant differences in differentiation grade, ER and HER2 status were found. PR-status was more often positive in the RRSO group without reaching statistical significance (38% vs. 13%, P = 0.07). Median DT in the RRSO group was 124 days (range 89-193) and 93 days (range 54-253) in the non-RRSO group (P = 0.47). Conclusion BC occurring after RRSO in BRCA mutation carriers features a lower MAI, suggesting a less aggressive biological behavior. When confirmed in larger series, this may have consequences for BC screening protocols for BRCA1/2 mutation carriers after RRSO. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-05-05.