Kanae Nosaka

Expression of minichromosome maintenance 7 (MCM7) in small lung adenocarcinomas (pT1): Prognostic implication.

Minichromosome maintenance (MCM) proteins, essential molecules in the initiation and elongation of DNA replication, have been considered to be good indicators of cell proliferation. We examined the expressions of MCM7 and Ki-67 in lung adenocarcinomas (ACs) with a diameter less than 3cm (pT1), to clarify their pathobiological significance. Immunohistochemistry was conducted to obtain labeling indices (LIs%) for MCM7, MCM2 and Ki-67 in 100 surgically removed pT1 ACs. The LIs were compared with clinicopathological profiles and overall survival rates. The mean LIs of MCM7 and Ki-67 were 20.2+/-15.2% and 13.7+/-11.2%, the value being higher in the former than in the latter (P<0.01). MCM7 LIs were significantly correlated with sex, histological grade, histological subtype, tumor size, LIs of Ki-67, MCM2 and P53 (P<0.05). LIs of MCM7 and Ki-67 were significantly higher in the 84 non-bronchioloalveolar carcinomas than in the 16 bronchioloalveolar carcinomas (P<0.01). Kaplan-Meier survival curves showed that patients with higher MCM7 LIs had poorer prognosis in the 100 pT1 ACs as well as in the 73 stage I ACs. Multivariate Cox regression analysis confirmed that the LIs of MCM7, but not the LIs of MCM2 and Ki-67, was an independent prognostic marker in the 73 stage I ACs. These results suggest that MCM7 is an independent prognostic marker, being more reliable than MCM2 or Ki-67 in human pT1 ACs as well as in human stage I ACs.

Minichromosome maintenance-7 and geminin are reliable prognostic markers in patients with oral squamous cell carcinoma: immunohistochemical study

BACKGROUND Minichromosome maintenance (MCM) proteins act as the origin licensing machinery that regulates initiation of DNA replication. Geminin is a licensing repressor and prevents reinitiation of DNA replication by blocking reloading of MCM proteins at replication origins. Recent studies have proposed that MCM7 and geminin may be sensitive proliferative and prognostic markers of various malignant tumors. This study aimed to analyze the expression of MCM7 and geminin to clarify pathobiological significance in human oral squamous cell carcinomas (OSCCs). METHODS We performed immunohistochemical analysis on 10 specimens of normal oral epithelia, 50 lesions with dysplasia and 113 OSCCs. Labeling indices (LIs) for MCM7, geminin and Ki-67 were evaluated, comparing with clinicopathological profiles. RESULTS The mean LIs for MCM7 were 29.2% for normal epithelia, 32.2% for dysplasias, and 51.1% for OSCCs; the value was significantly higher in the last than in the former two (P < 0.01). The mean LIs for geminin were 6.8% for normal epithelia, 9.2% for dysplasias, and 21.3% for OSCCs; the value was significantly higher in the OSCCs (P < 0.01). The MCM7 LIs were correlated with the histological grade of OSCCs, in which the highest LIs were noted in the poorly differentiated type (P < 0.01). The survival rate was significantly lower in patients with a higher MCM7 LI (>49.5%) than in those with a lower LI (P < 0.05) at stage III-IV. However, the survival rate in the patients with a higher geminin LI (>19.5%) was significantly higher than in those with a lower LI (P < 0.05) at stage IV.

Geminin, Ki67, and minichromosome maintenance 2 in gastric hyperplastic polyps, adenomas, and intestinal-type carcinomas: pathobiological significance.

BackgroundGeminin negatively regulates Cdt1 and induces the formation of prereplicative complexes by loading mini-chromosome maintenance proteins (Mcm) onto chromatin and limiting DNA replication to once per cell cycle. Recent studies have suggested that geminin expression is a marker of the S/G2/M phase of the cell cycle and is associated with a poor prognosis in various human malignancies. This study aimed to clarify the pathobiological role of geminin in intestinal-type gastric carcinoma, and its relationships with minichromosome maintenance 2 (Mcm2) and Ki67 expression.MethodsWe performed western blot analysis of seven human gastric cancer cell lines, and immunohistochemical analysis of 72 gastric mucosal lesions and 128 surgically removed advanced intestinal-type gastric carcinomas. Double-labeling immuno-fluorescence was performed to identify the coexpression of geminin and Ki67.ResultsGeminin was detected in all cell lines. Geminin labeling indices (LIs) in hyperplastic polyps, low-grade adenomas, high-grade adenomas, and intestinal-type adenocarcinomas were 3.9%, 10.5%, 18.6%, and 27.2%, respectively. The equivalent LIs for Ki67 and Mcm2 were 17.7%, 42.2%, 52.6%, and 59.7%; and 26.7%, 70.0%, 67.8%, and 77.8%, respectively. Double-labeling immunofluorescence revealed coexpression of geminin and Ki67 in both normal and tumor cells. The LI for geminin was significantly correlated with N stage, International Union Against Cancer (UICC) stage, Mcm2 LI, and Ki67 LI. Patients in stages I-IV and stage III with higher LIs for geminin (>25%) had significantly worse prognoses (P < 0.05 and P < 0.04, respectively). Univariate Cox regression analysis indicated that the overall survival of stage I-IV tumors was significantly correlated with high geminin LIs (relative risk [RR] = 1.94; P = 0.04).ConclusionsGeminin expression might reflect the biological nature of gastric intramucosal neoplasms and could be a possible prognostic marker in advanced intestinal-type gastric carcinomas.

MR imaging findings of mass-forming endosalpingiosis in both ovaries: a case report.

A 50-year-old postmenopausal woman, who underwent ultrasonography at a periodic medical checkup, was found to have bilateral ovarian masses. Pelvic magnetic resonance imaging (MRI) showed bilateral multilocular cystic ovarian masses. The cyst walls and septal structure demonstrated contrast enhancement. She underwent bilateral salpingo-oophorectomy. Microscopic examination revealed that the cysts were lined with cuboidal or columnar epithelial cells, and some of the cells were ciliated. The final histopathological diagnosis was endosalpingiosis. Endosalpingiosis is defined as the presence of ectopic ciliated epithelium, resembling the normal endosalpinx, without endometrial stroma. It rarely presents as a tumor-like mass on MRI.

Clinicopathologic Diversity of Undifferentiated Sarcoma With : Analysis of 11 Cases With a Reappraisal of the Utility of Immunohistochemistry for Bcor and Ccnb3 bcor-ccnb3 : Analysis of 11 Cases With a Reappraisal of the Utility of Immunohistochemistry for Bcor and Ccnb3 Fusion: Analysis of 11 Cases With a Reappraisal of the Utility of Immunohistochemistry for Bcor and Ccnb3

Undifferentiated sarcoma harboring the BCOR-CCNB3 fusion is characterized by its predilection to affect skeletons of adolescent males, cellular small round/spindle cell morphology, and CCNB3 immunoreactivity. We analyzed 11 cases of BCOR-CCNB3 sarcoma, 10 of which were identified in a reverse transcription-polymerase chain reaction–based screen of 85 patient samples recorded in our database as unclassified small round or spindle cell sarcomas. BCOR rearrangements were confirmed by fluorescence in situ hybridization in 8 tumors. All patients were males aged between 6 and 31 years. In addition to 5 tumors in soft tissue and 4 in the axial or appendicular skeletons, which are typical locations, a tumor was located in the paranasal sinus and another in the lung. Microscopically, the tumors comprised proliferating atypical spindle and/or small round cells with diverse morphologic features such as small concentric whorls, myxoid stroma, a hemangiopericytomatous appearance, and/or hyalinized collagen resembling a solitary fibrous tumor, and angiomatous or slit-like spaces containing extravasated erythrocytes. Tumor cells were immunoreactive to CCNB3 (9/11), BCOR (10/10), TLE1 (6/10), bcl-2 (9/11), CD99 (8/10), CD56 (8/10), c-kit (4/10), and cyclin D1 (10/10). In an immunohistochemical analysis of an additional 412 small round or spindle cell tumors, CCNB3 was detected in 6 (1.5%) and BCOR in 18 (4.4%). Our analysis highlights the varying clinicopathologic features of this tumor, which partially overlap with other small round or spindle cell tumors, including solitary fibrous tumor and vascular tumors. Because CCNB3 and BCOR immunohistochemistry lacks adequate sensitivity and specificity, a molecular genetic approach remains essential for diagnosis.

Cytoplasmic maspin expression is a predictor of poor prognosis in patients with lung adenocarcinoma measuring <3 cm

Maspin is known to be a tumour suppressor protein, and few studies focused upon its prognostic significance in patients with small‐size lung adenocarcinoma have been reported; however, its clinical significance remains controversial. We explored the prognostic value of maspin with particular reference to its subcellular localization in patients with resected lung adenocarcinoma measuring <3 cm.

Cytoplasmic maspin expression predicts poor prognosis of patients with soft tissue sarcomas

BackgroundMaspin is a 42 kDa protein known to act as a tumor suppressor. Although its function has not been fully elucidated, numerous reports have investigated the prognostic impact of maspin in patients with several types of cancer. However, there have been no reports on the association between maspin expression and the prognosis of patients with soft tissue sarcomas (STS). The aim of this study was thus to explore the association of maspin expression with the prognosis of patients with STS.MethodsOne-hundred and eight paraffin-embedded STS tissue samples were immunohistochemically analyzed using antibodies for maspin and Ki-67 antigen. The patients were followed up for 1 to 300 months (median: 33 months) and the prognostic value was evaluated by log-rank test and Coxs regression hazard model.ResultsCytoplasmic maspin expression was observed in 48.1% of specimens, and was significantly correlated with a higher FNCLCC grade (P = 0.002) and the presence of distant metastases (P = 0.001), and those with cytoplasmic maspin expression had both shorter disease-free survival (DFS) and overall survival (OS) by log-rank test (P <0.001, P = 0.001, respectively). By Coxs multivariate analysis, the presence of distant metastases was the only prognostic factor for DFS and OS.ConclusionsThis is the first report to reveal an association between maspin expression and the prognosis of patients with STS. Although further studies with a larger series of patients and a longer follow-up period will be needed, cytoplasmic maspin expression could be an indicator of unfavorable prognosis in patients with STS.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_205

Podoplanin expression in cancer-associated fibroblasts predicts unfavourable prognosis in patients with pathological stage IA lung adenocarcinoma.

Podoplanin expression in cancer‐associated fibroblasts (CAFs) has been proposed as an unfavourable indicator in squamous cell carcinoma of the lung, but little is known about its clinical significance in early‐stage lung adenocarcinoma. We evaluated the prognostic impact of podoplanin expression in patients with pathological stage (p‐stage) IA lung adenocarcinoma as categorised by the 8th edition of the tumour–node–metastasis classification for lung cancer.

Cytoplasmic expression of maspin predicts unfavourable prognosis in patients with squamous cell carcinoma of the lung

Maspin is known to be a tumour suppressor protein, and its prognostic significance in patients with several types of cancer, including lung squamous cell carcinoma (SCC), has been reported. However, its prognostic impact on lung SCC has been controversial. We explored the prognostic value of maspin expression with particular reference to its subcellular localization in patients with lung SCC.

A Small Granulosa Cell Tumor of the Ovary Incidentally Detected on Diffusion-weighted Images

A left cystic ovarian tumor was identified during physical examination of a 72-year-old woman. Pelvic MRI showed a multilocular cystic mass of the left ovary, which was suspected to be a serous cystadenoma. Moreover, an unexpected 10-mm nodular hyperintensity in the right ovary was observed on diffusion-weighted images (DWI), with hypointensity on the apparent diffusion coefficient (ADC) map, isointensity on T1-weighted images (T1WI) and fat-suppressed T1WI, and hyperintensity on T2WI compared to the myometrium (Fig. 1). We could not rule out a malignant solid ovarian tumor. Bilateral adnexectomy was performed. Microscopy showed a left ovarian serous cystadenoma and a small right ovarian tumor. The right tumor cells, with pale eosinophilic cytoplasm, grew in solid pattern with fibrous stroma. Nuclear grooves were occasionally observed. Nuclear atypia was inconspicuous, with mitotic count of 1/1-2HPF. Tumor cells were positive for inhibin (Fig. 2) on immunohistochemistry. The tumor was diagnosed as an adult granulosa cell tumor. DWI reveals malignant lesions through its excellent tissue contrast due to the hypercellularity. It can clearly demonstrate the anatomic extent of disease, including the myometrial invasion depth of endometrial carcinoma, parametrial invasion in cervical carcinoma, and venous tumor thrombus in endometrial stromal sarcoma, and it can also easily visualize metastatic peritoneal lesions. Here, DWI revealed an unexpected contralateral ovarian tumor, which was unclear in other conventional images. In reproductive age, ovaries frequently exhibit hyperintensity on DWI, with increased ADC values (1.67–1.71 × 10−3 mm2/s).1 After menopause, ovary signals are reduced on T2WI because of atrophy, decreasing follicles, and increasing numbers of stromal cells.2 Similarly, the signal intensity of DWI is decreased. Therefore, nodular hyperintensity on DWI with low ADC values may indicate malignant solid ovarian tumors. In reproductive case, it is also necessary to evaluate carefully whether nodular hyperintensity on DWI is consistent as a normal ovary or other benign lesions such as hemorrhagic cyst and endometrioma, because it can affect patient management.