Investigation of the usefulness of a bile duct biopsy and bile cytology using a hyperspectral camera and machine learning.

To improve the efficiency of pathological diagnoses, the development of automatic pathological diagnostic systems using artificial intelligence (AI) is progressing; however, problems include the low interpretability of AI technology and the need for large amounts of data. We herein report the usefulness of a general-purpose method that combines a hyperspectral camera with machine learning. As a result of analyzing bile duct biopsy and bile cytology specimens, which are especially difficult to determine as benign or malignant, using multiple machine learning models, both were able to identify benign or malignant cells with an accuracy rate of more than 80% (93.3% for bile duct biopsy specimens and 83.2% for bile cytology specimens). This method has the potential to contribute to the diagnosis and treatment of bile duct cancer and is expected to be widely applied and utilized in general pathological diagnoses.

A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis.

The tumourigenesis of early lung adenocarcinomas, including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic predominant invasive adenocarcinoma (LPA), remains unclear. This study aimed to capture disease-related molecular networks characterising each subtype and tumorigenesis by assessing 14 lung adenocarcinomas (AIS, five; MIA, five; LPA, four). Protein-protein interaction networks significant to the three subtypes were elucidated by weighted gene co-expression network analysis and pairwise G-statistics based analysis. Pathway enrichment analysis for AIS involved extracellular matrix proteoglycans and neutrophil degranulation pathway relating to tumour growth and angiogenesis. Whereas no direct networks were found for MIA, proteins significant to MIA were involved in oncogenic transformation, epithelial-mesenchymal transition, and detoxification in the lung. LPA was associated with pathways of HSF1-mediated heat shock response regulation, DNA damage repair, cell cycle regulation, and mitosis. Genomic alteration analysis suggested that LPA had both somatic mutations with loss of function and copy number gains more frequent than MIA. Oncogenic drivers were detected in both MIA and LPA, and also LPA had a higher degree of copy number loss than MIA. Our findings may help identifying potential therapeutic targets and developing therapeutic strategies to improve patient outcomes.

An extremely rare case of neuromuscular and vascular hamartoma of the appendix.

BACKGROUND: Neuromuscular and vascular hamartoma is a rare lesion of the small intestine, with only 26 cases reported since its initial description in 1982. No occurrence of hamartoma in the appendix has been reported until now. CASE PRESENTATION: A 60-year-old man had been suffering from longstanding right lower quadrant pain. Abdominal computed tomography showed a slight swelling of the appendix as the possible cause of his pain. Laparoscopic appendectomy with partial resection of the cecum was performed for diagnostic and therapeutic purposes. An 18 × 10-mm lesion located on the tip of the appendix was found in the resected specimen. Pathological examination showed that the lesion was covered with normal mucosa and consisted of adipose tissue, smooth muscle fibers, small vessels, and neural fibers. These findings were consistent with neuromuscular and vascular hamartoma of the appendix. CONCLUSION: This is the first report of neuromuscular and vascular hamartoma arising from the appendix.

Disease-related cellular protein networks differentially affected under different EGFR mutations in lung adenocarcinoma.

It is unclear how epidermal growth factor receptor EGFR major driver mutations (L858R or Ex19del) affect downstream molecular networks and pathways. This study aimed to provide information on the influences of these mutations. The study assessed 36 protein expression profiles of lung adenocarcinoma (Ex19del, nine; L858R, nine; no Ex19del/L858R, 18). Weighted gene co-expression network analysis together with analysis of variance-based screening identified 13 co-expressed modules and their eigen proteins. Pathway enrichment analysis for the Ex19del mutation demonstrated involvement of SUMOylation, epithelial and mesenchymal transition, ERK/mitogen-activated protein kinase signalling via phosphorylation and Hippo signalling. Additionally, analysis for the L858R mutation identified various pathways related to cancer cell survival and death. With regard to the Ex19del mutation, ROCK, RPS6KA1, ARF1, IL2RA and several ErbB pathways were upregulated, whereas AURK and GSKIP were downregulated. With regard to the L858R mutation, RB1, TSC22D3 and DOCK1 were downregulated, whereas various networks, including VEGFA, were moderately upregulated. In all mutation types, CD80/CD86 (B7), MHC, CIITA and IFGN were activated, whereas CD37 and SAFB were inhibited. Costimulatory immune-checkpoint pathways by B7/CD28 were mainly activated, whereas those by PD-1/PD-L1 were inhibited. Our findings may help identify potential therapeutic targets and develop therapeutic strategies to improve patient outcomes.

Differential Proteomic Analysis between Small Cell Lung Carcinoma (SCLC) and Pulmonary Carcinoid Tumors Reveals Molecular Signatures for Malignancy in Lung Cancer.

PURPOSE: The molecular underpinnings that may prognosticate survival and increase our understanding of tumor development and progression are still poorly understood. This study aimed to define the molecular signatures for malignancy in small cell lung carcinoma (SCLC), which is known for its highly aggressive clinical features and poor prognosis. EXPERIMENTAL DESIGN: Using clinical specimens, the authors perform a comparative proteomic analysis of high-grade SCLCs and low-grade pulmonary carcinoid tumors (PCTs), both of which are types of neuroendocrine tumors. A label-free LC-MS-based quantitative proteomic analysis is applied to tumor cells laser-microdissected from their formalin-fixed paraffin-embedded (FFPE) tissues obtained from six patients each. RESULTS: Overall, 1991 proteins are identified from tumor cells in the FFPE tissues. Through the protein-protein interaction network analysis of 201 proteins significantly, the authors find that SCLC is functionally characterized by activation of molecular pathways for spliceosome, RNA transport, and DNA replication and cell cycle. Particularly, 11 proteins involved in tumor proliferation (MCM2, 4, 6, 7, and MSH2), metastasis (RCC2, CORO1C, CHD4, and IPO9), and cancer metabolism (PHGDH and TYMP) are identified as SCLC-specific proteins. Furthermore, their prognostic significances are demonstrated by online Kaplan-Meier survival analysis. CONCLUSIONS AND CLINICAL RELEVANCE: These clinical tissue proteomic approach for SCLC reveals the proteins associated with aggressiveness and poor prognosis. The identified SCLC-specific proteins represent potential therapeutic targets. Moreover, MCMs and PHGDH can be poor prognostic factors for lung cancer.

Nuclear inverse polarity papillary lesions lacking myoepithelial cells: A report of two cases.

Here, cases of a 68- (Case 1) and a 44-year-old (Case 2) female are presented. They had an abnormality in the breast, and came to our hospital for further examination and treatment. Radiologically, malignancy could not completely excluded so breast excision was performed. Histologically, both cases revealed papillary neoplastic lesions lined by fibrovascular core and nuclear inverse polarity without atypia. Loss of myoepithelial cells was observed by HE, p63, and calponin. Previous report indicate CK5/6, ER, p63 and MUC3 are important for distinguishing between papillary lesions according to the differential index (based on Allred score) of ([ER total score] + [MUC3 total score])/([CK5/6 total score] + [p63 total score] + 1). Based on this analysis, our two cases had benign lesions. However, based on immunopositivity for cell-cycle marker Cyclin-D1, Case 1 was negative, and Case 2 was about 70% positive. Additionally, the Ki-67 index was <1% in both cases, and no evidence of disease was observed after a maximum 62 months of follow-up in both cases, despite lack of additional treatment. Thus, we propose that lack of myoepithelial cells in papillary lesions do not necessarily indicate malignancy and are thought to be, at the most, uncertain malignant potential.

Accuracy of the cobas EGFR Mutation Assay in Non-small-cell Lung Cancer Compared With Three Laboratory-developed Tests.

BACKGROUND: The reliability of the cobas EGFR assay to detect epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) as an in vitro diagnostic test was compared with 3 laboratory-developed tests (LDTs). MATERIALS AND METHODS: After screening for EGFR mutations using formalin-fixed-paraffin-embedded NSCLC tissue sections using the cobas EGFR assay, 151 samples were further tested with 3 LDTs; the peptide nucleic acid-locked nucleic acid polymerase chain reaction (PCR) clamp, PCR invader, and Cycleave assays. The cobas EGFR assay performance was evaluated by determining the concordance rate and κ-coefficient between the assays. In samples exhibiting discrepancies in the EGFR mutation status in the 4 assays, next-generation sequencing was performed to confirm mutated sequences. RESULTS: Concordance rates and κ-coefficients between the cobas EGFR assay and the other tests were 96.0% and 0.921 for the peptide nucleic acid-locked nucleic acid PCR clamp assay, 94.0% and 0.881 for the PCR invader assay, and 96.7% and 0.934 for the Cycleave assay, respectively. Data showed very good agreement with the other assays. Precise mutated sequences or exons in the EGFR gene matched in 137 samples (90.7%). Different results were obtained in 4 samples (2.6%), owing to systemic limitations of the assay. Next-generation sequencing of 10 (6.6%) samples with discordant results exhibited a concordance rate of 60% to 80% in each assay. CONCLUSIONS: The cobas EGFR assay showed high concordance rates and κ-coefficients between the 3 compared LDTs and can be used to select patients who would benefit from EGFR-tyrosine kinase inhibitors.

A Case of Congenital Infantile Fibrosarcoma of the Bowel Presenting as a Neonatal Intussusception.

Neonatal intussusception of the intestinal tract is rare. However, most neonatal intussusceptions have an organic lead point. For the lead point to be a neoplasm is extremely rare. We report a case that presented with neonatal intussusception with a congenital infantile fibrosarcoma as the lead point. The detection of ETV6-NTRK3 gene fusion was useful, although the definitive diagnosis was achieved by a comprehensive evaluation including this gene analysis, standard histology and immunohistochemistry. Neonatal intussusception should be suspected to be caused by a neoplasm. If pathological diagnosis is difficult, molecular analysis should be utilized to diagnose congenital infantile fibrosarcoma.

Glycan profiling using formalin-fixed, paraffin-embedded tissues: Hippeastrum hybrid lectin is a sensitive biomarker for squamous cell carcinoma of the uterine cervix.

AIM: Glycosylation of proteins is altered in cancer cells and distinctive glycan structures are associated with specific cancers, but little is known about the complete glycan profile of particular tumors. In this study, glycomic analysis of squamous cell carcinoma (SCC) of the uterine cervix was performed to search for useful markers. METHODS: A lectin microarray containing 45 lectins with different binding preferences that covered N- and O-linked glycans was coupled with evanescent field-activated fluorescent detection for glycomic analysis of SCC and normal squamous epithelium (NSE) of the cervix. Formalin-fixed, paraffin-embedded tissue specimens were obtained from 16 patients with uterine cervical cancer. Sections that included both tumor and non-tumor tissues were examined to detect alterations of glycans based on the lectin-binding pattern. RESULTS: Hippeastrum hybrid lectin was found to be a sensitive marker for distinguishing SCC of the cervix from NSE. It was the best lectin for discriminating SCC from other tissues according to receiver-operator curve analysis, as it showed a high sensitivity (81.8%), a high specificity (70.1%), and a large area under the curve (0.8182). Histochemistry confirmed specific cytoplasmic staining of SCC cells by Hippeastrum hybrid lectin, while there was little staining of cervical intraepithelial neoplasia and no staining of NSE. CONCLUSION: The present lectin microarray technique could be applied for tissue-based glycomic analysis of various tumors and for discovery of glycan-related biomarkers.

Clinicopathological Significance of TARBP2, APP, and ZNF395 in Breast Cancer.

The double-stranded RNA-binding protein TARBP2 has been suggested to act as an upstream regulator of breast cancer metastasis by destabilizing transcripts of the possible metastasis suppressors amyloid precursor protein (APP) and ZNF395. We examined this hypothesis by immunostaining of TARBP2, APP, and ZNF395 in 200 breast cancer specimens using tissue microarrays and analyzed the relationships between expression levels and clinicopathological parameters and prognosis. Increased TARBP2 overexpression was associated with shorter overall survival and disease-free survival, and increased but not reduced APP expression correlated with lower overall survival and disease-free survival. ZNF395 expression levels had no prognostic value, but reduced expression correlated with reduced lymph node metastasis. There was no significant relationship between TARBP2 overexpression and reduced APP and/or ZNF395 expression. Patients with tumors with higher TARBP2 or APP expression had unfavorable prognoses. Although reduced ZNF395 expression was significantly related to reduced lymph node metastasis, further studies are needed to clarify the role of TARBP2/APP/ZNF395 in breast cancer.

Epidermal growth factor receptor mutations in adenocarcinoma in situ and minimally invasive adenocarcinoma detected using mutation-specific monoclonal antibodies.

OBJECTIVES: Epidermal growth factor receptor (EGFR) mutation rates in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) were studied using both DNA analysis and mutation-specific immunohistochemistry. MATERIALS AND METHODS: The peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method was used to detect mutations in exons 18, 19, 20, and 21 of the EGFR gene in DNA samples extracted from paraffin-embedded tissue sections. Simultaneously, immunohistochemical analysis with two EGFR mutation-specific monoclonal antibodies was used to identify proteins resulting from an in-frame deletion in exon 19 (E746_A750del) and a point mutation replacing leucine with arginine at codon 858 of exon 21 (L858R). RESULTS: Forty-three tumors (22 AIS and 21 MIA) were examined. The EGFR mutation rate in AIS detected by DNA analysis was 27.3% (L858R, 5/22; exon 19 deletion,1/22), whereas that detected in MIA was 42.9% (L858R,4/21; exon 19 deletion,5/21). Mutations detected by immunohistochemical analysis included 22.7% (L858R, 4/22; exon 19 deletion, 1/22) in AIS and 42.9% (L858R, 4/21; exon 19 deletion, 5/21) in MIA. Although some results were contradictory, concordant results were obtained using both assays in 38 of 43 cases (88.4%). CONCLUSION: DNA and immunohistochemical analyses revealed similar EGFR mutation rates in both MIA and AIS, suggesting that mutation-specific monoclonal antibodies are useful to confirm DNA assay results.

Can synaptophysin be used as a marker of breast cancer diagnosed by core-needle biopsy in epithelial proliferative diseases of the breast?

The differential diagnosis of epithelial proliferative disease using core needle biopsy (CNB) is problematic because it is difficult to differentiate between intraductal papilloma, ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Many studies have reported that breast cancer lesions are positive for neuroendocrine (NE) markers, whereas only a small number of studies have reported immunopositivity for NE markers in normal mammary tissues or benign lesions. We asked whether NE factors could be used as markers of breast cancer. We determined the immunopositivity rate of synaptophysin, an NE marker, in 204 lesions excised from the breast using CNB in patients who visited a university-affiliated comprehensive medical facility and examined whether synaptophysin is a marker of breast cancer. The specimens were classified as synaptophysin-negative cases (56 benign, 99 malignant); equivocal cases (<1 %: 2 benign, 15 malignant); and synaptophysin-positive cases (1 benign, 31 malignant). The sensitivity, specificity, positive predictive value, and negative predictive value for malignancy of the lesions classified as synaptophysin positive were 23.3 %, 98.2 %, 96.9 %, and 36.1 %, respectively. The respective values for lesions classified as equivocal were 11.6 %, 96.6 %, 88.2 %, and 36.1 %. Synaptophysin may provide a marker of breast cancer diagnosed by CNB.

Comparison between Ki67 labeling index determined using image analysis software with virtual slide system and that determined visually in breast cancer.

BACKGROUND: In recent papers, Ki67 labeling index (LI) has been used to classify breast cancer patients into the low and high Ki67LI groups for comparison studies, which showed significant differences in many prognostic factors. It has not been clarified whether image analysis software can be used for calculating LI in breast cancer. In our study, we examined whether Ki67LI in breast cancer calculated using image analysis software correlates with that measured on the basis of visual. METHODS: Fifty patients were randomly selected among breast cancer patients who underwent surgical operation from March, 2010 to May, 2010 in our hospital without preoperative chemotherapy. In this study, for the virtual slide system (VSS: VS120-L100, Olympus, Tokyo, Japan), the high-resolution VSs of all the 50 patients were prepared as samples. The image analysis software use for calculating LI was Tissuemorph Digital Pathology (Tissuemorph DP: Visiopharm, Hoersholm, Denmark). The calculated LI was extracted from 3 to 5 views containing hot spots. The LI calculated using Tissuemorph DP was designed as LI/image/T. The digital image of 3 to 5 LI/image/T views was printed out, and on the digital photograph, we counted visually the number of Ki67-immunopositive cells in exactly the same area, and the percentage of Ki67-immunopositive cells was designed as LI/direct. Moreover, a pathologist's assistant (PA) determined the tumor area in the same specimen using VSS and calculated LI using Tissuemorph DP, which was designed as LI/image/PA. The chief pathologist (CP) similarly calculated LI which was designed as LI/image/CP. We evaluated the degree of agreement between different data sets "LI/image/T and LI/direct" and "LI/image/T, LI/image/CP, and LI/image/PA" by using interclass correlation coefficient (ICC). RESULTS: The average counts of cells were as follows: LI/direct, 3209.7 ± 1970.4 (SD); LI/image/T, 2601.6 ± 1697.1; LI/image/PA, 2886.5 ± 2027.5; LI/image/CP, 18805.5 ± 22293.4. The values of LI/direct and LI/image/T showed almost perfect agreement as showed by an ICC of 0.885 (95 % CI, 0.806-0.933; p < 0.001). The agreement among three investigators was almost perfect. The obtained ICC was 0.825 (95 % CI, 0.739-0.890; p < 0.001) among the data of LI/image/T, LI/image/CP and LI/image/PA. There were five cases that immunopositivity for Ki67 showed a more than 10 % disagreement between LI/direct and LI/image/T. CONCLUSION: The merits of calculating Ki67 LI using Tissuemorph DP are as follows. First, the staining intensity of the cells to be counted can be adjusted. Second, the portion of a tumor including "hot spots" for counting can be chosen. Third, many cancer cells can be counted more rapidly using Tissuemorph DP than by visual observation. However, it is important that pathologist should check and carry out the final decision of the data, when Ki67 LI using Tissuemorph DP is calculated.

Association of IASLC/ATS/ERS Histologic Subtypes of Lung Adenocarcinoma With Epidermal Growth Factor Receptor Mutations in 320 Resected Cases.

BACKGROUND: The relationships between the subtypes defined by the new international histologic classification of lung adenocarcinoma (IASLC/ATS/ERS) and epidermal growth factor receptor (EGFR) mutations were studied. PATIENTS AND METHODS: We retrospectively reviewed 320 patients with lung adenocarcinoma (162 women, 158 men; mean age, 69 years) who had undergone complete resection, focusing on the new histologic subtypes and EGFR mutations. The clinical stage was IA in 196 patients, IB in 95, IIA in 10, IIB in 10, IIIA in 6, and IV in 3. RESULTS: The most prevalent subtype was papillary (35.0%), followed by acinar (29.4%), lepidic (13.1%), solid (7.2%), adenocarcinoma in situ (6.6%), minimally invasive adenocarcinoma (6.3%), micropapillary (1.6%), and invasive mucinous adenocarcinoma (1.0%). These subtypes were predictive for both postoperative disease-free and overall survival. EGFR mutations, detected in 40.6% of all cases, were most frequent in acinar (48.4%), followed by minimally invasive adenocarcinoma (45.0%) and papillary (43.8%). They were least frequent in the solid subtype (17.4%). EGFR mutation status did not affect postoperative disease-free or overall survival. CONCLUSION: The outcome after complete resection for lung adenocarcinoma was predicted by the proposed subtype classification. Because EGFR mutations were found in all subtypes, mutation analyses are essential to identify patients with postoperative relapse who would benefit from EGFR-tyrosine kinase inhibitor therapy.

Close association of IASLC/ATS/ERS lung adenocarcinoma subtypes with glucose-uptake in positron emission tomography.

OBJECTIVES: Correlations between maximum standardized uptake value (SUVmax) in fluorodeoxyglucose positron emission tomography (FDG-PET) and IASLC/ATS/ERS histopathologic subtypes of lung adenocarcinoma remain unclear. Therefore, the aim of this study was to retrospectively clarify associations between SUVmax and adenocarcinoma subtypes with postoperative outcomes. MATERIALS AND METHODS: Associations of SUVmax measured in preoperative FDG-PET/CT and histologic subtypes of lung adenocarcinoma resected in our hospital were analyzed retrospectively. Overall and disease-free survival rates after surgery were calculated by the Kaplan-Meier method, and survival differences between patient groups were tested by the log-rank test. Multivariate analysis for survival was performed using the Cox regression model. RESULTS: A total of 255 patients (130 men and 125 women; mean age, 69 years; range, 22-88 years) were included in the study. Clinical stages included IA in 151 patients, IB in 79, IIA in 9, IIB in 10, and IIIA in 6. SUVmax was closely associated with histologic subtype in resected specimens (p<0.0001). Values were highest in micropapillary predominant invasive adenocarcinoma (MPA) followed by solid predominant (SPA), invasive mucinous (IMA), acinar predominant (APA), papillary predominant (PPA), lepidic predominant (LPA), minimally invasive adenocarcinoma (MIA), and adenocarcinoma in situ (AIS). When the subtypes were classified into three subgroups [group A, AIS+MIA+LPA (low risk); group B, APA+PPA+IMA (intermediate risk); and group C, SPA+MPP (high risk)] by expected postoperative prognoses, there were significant differences in SUVmax among the subgroups corresponding to recurrence risk (p=0.0001). CONCLUSION: Preoperative SUVmax was closely associated with both adenocarcinoma subtype and aggregated subgroups, reflecting malignant grade of the tumor and prognosis.

Positive predictive value for malignancy of pure flat epithelial atypia diagnosis by percutaneous needle biopsy of the breast: management of FEA in ultrasonography.

BACKGROUND: Some reports suggest that the rate of definitive diagnosis of malignant tumors, namely, the final diagnosis being revised to a higher stage, in patients diagnosed as having flat epithelial atypia (FEA) by percutaneous needle biopsy of the breast (PNB) is as low as 0-3 %. However, other reports suggest that the rate is as high as 10 % or more, bringing confusion on this issue. We examined the positive predictive value for malignancy in the patients diagnosed as having pure FEA and the patients' radiolopathological characteristics observed in our hospital. METHODS: Of the patients who underwent PNB in our facility, those who were diagnosed as having pure FEA were recruited as the subjects of this study. RESULTS: Of the 4,197 consecutive patients who underwent PNB, 44 (1.0 %) were diagnosed as having pure FEA following a re-examination. Among 44 cases, 39 cases were selected as the subjects of this study. Among the 39 patients, six patients were diagnosed as having malignant lesions, two of whom had invasive carcinoma of no special type (papillotubular type), one had tubular carcinoma, one had ductal carcinoma in situ (DCIS) of high nuclear grade, one had DCIS of intermediate nuclear grade, and one had DCIS of low nuclear grade. The diameters of 6 malignant lesions were 10-30 mm at ultrasonography (US) examination. Five of the 39 patients had contralateral breast cancer. CONCLUSION: The positive predictive value for malignancy of pure FEA was 15.7 %. The patients with pure FEA may make a follow up without an excisional biopsy when the lesion sizes less than 10 mm on US examination.

Proteomic analysis of differential protein expression by brain metastases of gynecological malignancies.

Brain metastases of gynecological malignancies are rare, but the incidence is increasing. Patients with brain metastases have a poor prognosis, therefore early detection and optimal management is necessary. In order to determine a new biomarker, we aimed to identify proteins that associated with brain metastases. We investigated proteins associated with brain metastases of gynecological malignancies in three patients who underwent surgical resection (stage IIb cervical cancer, stage Ib endometrial cancer, and stage IIIb ovarian cancer). Proteomic analysis was performed on formalin-fixed paraffin-embedded (FFPE) samples of the primary tumors and brain metastases, which were analyzed by liquid chromatography with tandem mass spectrometry. Thereafter, candidate proteins were identified by the Scaffold system and Mascot search program, and were analyzed using western blotting and immunohistochemistry. As a result, a total of 129 proteins were identified. In endometrial and ovarian cancers, western blotting revealed that the expression of alpha-enolase (ENO1) and triosephosphate isomerase (TPI-1) was higher and the expression of Transgelin-2 (TAGLN2) was lower in metastatic tumors than in primary tumors. On the other hand, the expression of TPI-1 and TAGLN2 was lower in metastatic tumors than in primary tumors in cervical cancer. Immunohistochemistry confirmed that ENO1 expression was elevated in the metastatic tumors compared with the primary tumors. In conclusion, the present study showed that FFPE tissue-based proteomics analysis can be powerful tool, and these findings suggested that ENO1, TPI-1, and TAGLN2 may have a role in the development and progression of brain metastasis from gynecological malignancies.

A significant imbalance in mitosis versus apoptosis accelerates the growth rate of sessile serrated adenoma/polyps.

Sessile serrated adenoma/polyps (SSA/Ps) of the colon are thought to be precursors of sporadic carcinomas. Although it is suggested that SSA/P may grow rapidly from the early stage, its cell kinetics remains obscure. To solve this problem, we analyzed the mitotic and apoptotic activity of normal crypts, microvesicular hyperplastic polyps (MVHPs), and tubular adenomas (TAs), using phospho-histone H3 and cleaved caspase 3 immunohistochemistry. The mitotic index for SSA/Ps (mean, 5.63) and TAs (6.98) was significantly higher than those for normal crypts (2.72) and MVHPs (2.86). Of all tested lesions, the apoptotic index was lowest for SSA/Ps (0.96; normal, 2.71; MVHPs, 2.62; TAs, 6.01) with statistically significant differences. The net growth ratio was close to 1.0 in normal crypts (1.07) while remaining low in MVHPs (1.06) and TAs (1.38), but was markedly elevated in SSA/Ps (7.32, P < 0.01) due to the large imbalance between mitosis and apoptosis. As to apoptosis regulatory proteins, expression of anti-apoptotic Bcl-2 was significantly reduced or undetectable in MVHPs and SSA/Ps, while TAs showed stronger staining than normal crypts. Expression of pro-apoptotic Bax and its activators, Bim and Bad, was significantly reduced in MVHPs and SSA/Ps. We suggest that other complex mechanisms may act synergistically with Bax, Bim, or Bad deficiency to regulate apoptosis suppression in SSA/Ps.

A primary pulmonary glomus tumor: a case report and review of the literature.

A case of a glomus tumor originating from the lung is reported. A 43-year-old female had undergone resection of a right lung tumor following a clinical diagnosis of carcinoid, sclerosing hemangioma, or other sarcoma. Histologically, the tumor comprised uniform small round to oval cells with centrally located nucleus, a clear cytoplasm, and apparent cell borders. The tumor also showed a focally hemangiopericytomatous pattern with irregularly branching or dilated vessels. Electron microscopy revealed smooth muscle differentiation of the tumor cells. Immunostaining further revealed that the tumor cells expressed smooth muscle actin, h-caldesmon, muscle specific actin (HHF-35), but not cytokeratin, epithelial membrane antigen, synaptophysin, or chromogranin A. Based on these findings, a diagnosis of primary pulmonary glomus tumor was established. Glomus tumors of the lung are very rare and only 21 cases have been reported to date. The histological features of the present tumor and the relevant literature are discussed.