Characteristics of vaginal microbiota in various cervical intraepithelial neoplasia: a cross-sectional study.

BACKGROUND: Precancerous lesions of cervical cancer exhibit characteristics indicative of natural progression. To prevent overtreatment of patients whose cervical intraepithelial neoplasia (CIN) in regression and to predict the onset of invasive cervical cancer at an early stage, we've identified the vaginal microbiome as a potential key factor, which is associated with both HPV infection and the various cervical intraepithelial neoplasia. This study aims to investigate the microbiome characteristics of patients with various cervical intraepithelial neoplasia. METHODS: Utilizing high-throughput 16S ribosomal RNA (16S rRNA) sequencing technology, a description of the characteristics and community composition of Vaginal Microbiota (VMB) was conducted among 692 Chinese women infected with the High-risk Human Papillomavirus (HR-HPV). RESULTS: As the grade of the lesions increased, the proportions of Lactobacillus and Pseudomonas demonstrated a significant declining trend, while the proportions of Gardnerella, Dialister, and Prevotella significantly increased. The diversity of the VMB was more significant in high-grade CIN. Furthermore, KEGG pathway enrichment analysis indicates that high-grade cervical intraepithelial neoplasia can inhibit various pathways, including those of phosphotransferase system, transcription factors, Fructose and mannose metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism, which may contribute to the development of early cervical cancer symptoms. CONCLUSION: Patients with CIN exhibit a distinct vaginal microbial profile characterized by a decrease in Lactobacillus and Pseudomonas, and an increase in Gardnerella, Prevotella, and Dialister. The proliferation and diminution of these two types of microbial communities are interrelated, suggesting a mutual restraint and balance among them. Disruption of this regulatory balance could potentially lead to the onset of cervical lesions and carcinogenesis. Retrospectively registered: This study was approved by the Ethics Committee of the Beijing Chaoyang Hospital affiliated with the Capital Medical University (NO.2023-S-415).

[Morphologic features suggestive of submucosal invasive adenocarcinoma in colorectal mucosal biopsy specimens].

OBJECTIVE: To observe and summarize the morphologic features that may suggest submucosal invasive adenocarcinoma in colorectal mucosa biopsy specimens. METHODS: The study cohort included 432 colorectal biopsy specimens were obtained from 2006 to 2012. All the cases had radical surgery. Basing on the pathologic diagnoses, the cases were divided into 366 invasive adenocarcinoma (IAC) and 66 high-grade intraepithelial neoplasms (HGIN). These two groups were compared. RESULTS: In the IAC group, the percentage of tumor forming cribriform structures, acute angle-shaped glands, diffuse carcinoma cell proliferation was 61.2% (224/366) , 33.8% (124/366) and 7.4% (27/366) , respectively. In the HGIN group, cribriform gland structures appeared in 6.0% (4/66) of the cases, while no acute angle-shaped gland or diffuse carcinoma cell proliferation was detected. The difference of these three characteristics in the two group was statistically significant (all P < 0.01). Glandular branching was detected in 89.9% (329/366) of IAC cases and 66.7% (44/66) of HGIN cases; this difference was not significant. There was no difference in cellular atypia between the two groups. Interstitial fibrosis was detected more frequently in the IAC group (85.5%, 313/366 in IAC versus 0 in HGIN, P < 0.01). In biopsy specimens of IAC, a few cases showed neoplastic glands in close contact with large lymphatics, adipose tissue, and ganglion. CONCLUSIONS: In colorectal biopsy specimen, the five features that suggest submucosal invasion of the neoplastic glands including the formation of cribriform structure, angular gland, diffuse carcinoma cells, interstitial fibrosis and neoplastic glands in close contact with the thick-walled vessels.

[Expression of glucose transporter protein 1 and desmin in reactive mesothelial hyperplasia and epithelioid malignant mesothelioma].

OBJECTIVE: To investigate the expression of glucose transporter protein 1 (GLUT-1) and desmin in benign and malignant mesothelial lesions, including reactive mesothelial hyperplasia (RMH), epithelioid malignant mesothelioma (EMM) and metastatic adenocarcinoma (MAC). METHODS: One hundred and forty two pleural biopsy specimens were collected in this study, including 58 cases of RMH, 53 cases of EMM and 31 cases of MAC. Immunohistochemical EliVision method was performed to detect GLUT-1 and desmin expression. RESULTS: The positive rates for GLUT-1 in RMH, EMM and MAC were 13.8% (8/58) , 81.1% (43/53) and 77.4% (24/31) , respectively, with statistically significant differences between RMH and others (both P < 0.01). The positive rates for desmin in RMH, EMM and MAC were 77.6% (45/58) , 9.4% (5/53) and 0 (0/31) , respectively, with statistically significant difference between RMH and others (both P < 0.01). The combined expression pattern of positive GLUT-1 and negative desmin was found in 1 (1.7%, 1/58) RMH cases, 41 (77.4%, 41/53) EMM cases and 24 (77.4%, 24/31) MAC cases, with statistically significant difference between RMH and others (both P < 0.01). CONCLUSIONS: GLUT-1 and desmin may be used as immunohistochemical markers in separating RMH from EMM. Combined application of two antibodies may improve the specificity.

[Pulmonary capillary hemangiomatosis: a clinicopathologic analysis of 2 cases with review of literature].

OBJECTIVE: To investigate the clinicopathologic features of pulmonary capillary hemangiomatosis (PCH). METHODS: The clinical and pathologic profiles of 2 PCH cases were evaluated. Immunohistochemical study (EnVision method) was performed on fixed tissues. The biologic behavior was analyzed with follow-up data. RESULTS: The main presenting symptom was dyspnea. Chest radiography of the two cases depicted diffuse, ground-glass nodules, accompanied by enlarged central pulmonary arteries. Microscopically, the most distinctive feature was proliferation of capillary channels within pulmonary interstitium and alveolar walls, accompanied by muscularization of arterioles. Immunohistochemical study showed an abundance of mast cells in the lesion, and staining for platelet-derived growth factor receptor-beta (PDGFR-ß) localized to vascular smooth muscles surrounding the proliferating capillaries and the mast cells. The index of Ki-67 was less than 1 percent and the p53 was negative. CONCLUSIONS: PCH is a rare vascular proliferative disease of yang patients. Increased number of mast cell and the up-regulation of PDGFR-ß may suggest mechanism for PCH. The clinical and radiologic diagnosis of PCH can be very difficult, and the histological examination is regarded as the most reliable means to establish the diagnosis. Pathologists should improve their knowledge on PCH.

Effects of an evidence-based nursing intervention on prevention of anxiety and depression in the postpartum period.

Postpartum depression has been one of the most common psychological disorders in patients during postpartum period. The constant anxiety and depression during this period seriously affect the physiological and psychological health of both the mother and infant. Evidence-based nursing has been widely applied in clinical practice and has achieved remarkable results. However, the effect of evidence-based nursing on postpartum depression remains unclear. Pregnant women who were not diagnosed with postpartum depression during hospitalisation (Edinburgh Postpartum Depression Scale [EPDS] ≤ 13 points) but prone to postpartum depression (EPDS scores of 9-13) were recruited into the study. They were randomly divided into the Intervention group (N = 60) and Control group (N = 60). Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), EPDS and Pittsburgh Sleep Quality Index (PSQI) were used to investigate the psychological outcomes of puerperae during and after the 6-week intervention. Both the intention-to-treat and per-protocol analyses showed that 6 weeks of evidence-based nursing intervention significantly reduced the incidence of postpartum depression. The application of the evidence-based nursing also improved the patients' satisfaction degree and effectively alleviated their anxiety according to both the intention-to-treat and per-protocol analyses. Evidence-based nursing intervention had positive effects against anxiety and depression in the postpartum period.

Vimentin Protein In Situ Expression Predicts Less Tumor Metastasis and Overall Better Survival of Endometrial Carcinoma.

Background: Vimentin, a cytoplasmic intermediate filament protein, has been recently identified to be a prognostic biomarker in some cancers. However, the function of vimentin in endometrial carcinoma (EC) remains unclear. Our study aimed at evaluating vimentin expression in EC and preliminarily exploring the role of vimentin in EC progression. Methods: In total, 341 EC patients who underwent surgical follow-up were enrolled in the retrospective study. Vimentin expression levels in EC tissues were analyzed using immunohistochemistry. Furthermore, the vimentin (VIM) gene expression levels in 547 samples in The Cancer Genome Atlas (TCGA) were analyzed. To examine the prognostic value of vimentin in EC, Kaplan-Meier survival analysis was performed, and a Cox model was established. Gene set enrichment analysis (GSEA) was also conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to explore the role of vimentin in EC progression. Results: Negative vimentin expression in EC correlated significantly with lymph node metastasis, deep myometrium invasion (MI), lymph vascular space invasion (LVSI), advanced Federation International of Gynecology and Obstetrics Association (FIGO) stages (III and IV), and high tumor grade. Vimentin negativity was more common in type 2 EC than that in type 1 EC, and vimentin-negative patients had poorer overall survival compared with vimentin-positive patients. The results of GSEA suggested that vimentin may interact with classical pathways in EC. Conclusions: Negative vimentin expression correlates with tumor metastasis and worse overall survival in EC, suggesting that it may be an excellent prognostic biomarker for this disease. The mechanism by which vimentin contributes to EC progression needs to be explored in the future.

[Pathologic diagnosis and clinical analysis of chronic extrinsic allergic alveolitis].

OBJECTIVE: To study the clinicopathologic features and diagnostic approach of chronic extrinsic allergic alveolitis (EAA). METHODS: Seven cases of chronic EAA diagnosed by open lung biopsy or lung transplant were enrolled into the study. The clinical and pathologic features were analyzed and the literature was reviewed. RESULTS: There were altogether 4 men and 3 women. The age of the patients ranged from 30 to 65 years (mean = 48 years). All cases represented chronic form and five cases diagnosed by open lung biopsy also showed features of recent aggravation, leading to hospitalization. Four cases had known history of exposure to inciting gases, pollens and pets, and only 2 cases were positive for allergens. High-resolution CT scan showed ground-glass attenuation and reticular pattern that often had a patchy distribution and central predominance. Bronchoalveolar lavage analysis showed marked lymphocytosis, with CD4(+)/CD8(+) ratio less than 1. Lung function test demonstrated a restrictive ventilatory defect, with decreased compliance, reduced diffusion capacity and high airway obstruction. Five cases had open lung biopsy performed and two cases had undergone lung transplantation. Pathologic examination showed bronchiolocentric cellular interstitial pneumonia, interstitial fibrosis, non-caseating epithelioid granulomas, epithelioid histiocytic infiltrate in the respiratory bronchioles and intraluminal budding fibrosis. The five cases with open lung biopsy performed also showed neutrophilic infiltrate in the alveoli. The two lung transplant cases were complicated by severe fibrotic changes. CONCLUSIONS: Chronic EAA demonstrates characteristic pathologic features. Definitive diagnosis requires correlation with clinical and radiologic findings due to possible morphologic mimicry of other diffuse parenchymal lung diseases.

Effect of Nrf2 signaling pathway on the improvement of intestinal epithelial barrier dysfunction by hyperbaric oxygen treatment after spinal cord injury.

Disruption of the intestinal epithelial barrier following spinal cord injury (SCI) seriously affect long-term quality of life. Oxidative stress-induced epithelial cells' injury contributes to the epithelial barrier dysfunction. Hyperbaric oxygen (HBO) treatment has been proved to alleviate SCI. However, it is unclear whether or not HBO treatment affects intestinal barrier function following SCI. In this study, our purpose was to explore the impact of HBO treatment on intestinal epithelial barrier function and underlying mechanisms following SCI. An SCI model was established in rats, and the rats received HBO treatment. Intestinal injury, mucosal permeability, intercellular junction proteins, and oxidative stress indicators were evaluated in our study. We found that HBO treatment significantly alleviated intestinal histological damage, reduced mucosal permeability, and markedly prevented bacterial translocation. Furthermore, HBO treatment significantly increased the expression of Claudin-1 and E-cadherin, inhibited intestinal tissue oxidative stress as demonstrated by upregulation of superoxide dismutase and glutathione, and HBO downregulated malondialdehyde. Mechanically, we demonstrated that HBO treatment ameliorated intestinal oxidative stress possibly through upregulating nuclear factor E2-related factor 2 (Nrf2) and its downstream targets, Heme oxygenase-1(HO-1), NADH-quinone oxidoreductase-1(NQO-1), and glutamate cysteine ligase catalytic subunit (GCLC). These results suggested that HBO treatment triggered antioxidative effects against intestinal epithelial barrier dysfunction by promoting Nrf2 signaling pathway after SCI.

Diagnostic value of sialyl-Tn immunocytochemistry in breast cancer presenting with pathological nipple discharge.

BACKGROUND: Mucin-associated sialyl-Tn (sTn) antigen is overexpressed and related with adverse outcome in breast cancer (BC). The role of sTn in BC has not been well defined in pathological nipple discharge (PND) cytology. The authors examined sTn immunocytochemistry (ICC) in PND to determine whether it could be a biomarker of malignancy or aggressive disease. METHODS: PND was subjected to immunocytochemical staining for sTn antigen expression and thinprep cytology test (TCT) for enhancing the sensitivity and specificity. The examination data was compared with histological findings of subsequent biopsy specimens. Logistic regression analysis was used to determine which factors were most associated with malignant breast lesions. RESULTS: PND specimens were collected including 120 cases of intraductal papilloma, 24 cases of hyperplasia, 45 cases of ductal carcinoma in situ (DCIS), and 48 cases of invasive ductal carcinoma (IDC). STn ICC differentiated BC from benign intraductal lesions with a low sensitivity of 41.9% and a high specificity of 95.8%, but increased in combination with TCT to 64.5% and 100%, respectively. A high degree of concordance was observed between the results of sTn expression in cell smears and histological specimens. Moreover, the sTn expression was strongly associated with HER2-positive IDC (p = 0.039). Multivariate logistic analysis showed that positive sTn expression (OR: 14.241, 95%CI: 2.574, 78.794, p = 0.010) and accompanying mass (OR: 3.307, 95%CI: 1.073, 10.188, p = 0.037) were statistically significant independent risk factors for malignant PND. CONCLUSIONS: Mucin-associated sTn expression in PND cytology appears to be a reliable diagnostic marker for BC patients with the chief complaint of malignant nipple discharge and indicates a more aggressive behavior in IDC.

SR-B1 and CD10 combined immunoprofile for differential diagnosis of metastatic clear cell renal cell carcinoma and clear cell carcinoma of the ovary.

Both clear cell renal carcinoma (ccRCC) and clear cell carcinoma of the ovary (CCOC) have a clear cytoplasmic morphological feature, hence it is difficult to identify metastatic ccRCC and CCOC by morphology alone. At present, there are no effective immunohistochemical markers to distinguish between these two tumors. Studies have shown that the clear cytoplasm of ccRCC is mainly caused by cholesterol-rich lipids in the cytoplasm, while that of CCOC is due to the accumulation of cytoplasmic glycogen. OBJECTIVE: to hypothesize that the scavenger receptor class B-type 1 (SR-B1) protein responsible for HDL cholesterol uptake may be differentially expressed in ccRCC and CCOC, and high CD10 expression in the renal tubular epithelium may assist in distinguishing between ccRCC and CCOC. METHODS: effective immunohistochemical markers were applied in 90 cases of renal clear cell carcinoma and 31 cases of ovarian cancer to distinguish between the two types of tumors. RESULT: SR-B1 and CD10 expression is significantly higher in ccRCC than CCOC. Both SR-B1 and CD10 exhibited focal weak-medium intensity staining in CCOC, and their staining extent and intensity were significantly lower than ccRCC. The sensitivity and specificity of SR-B1 for identifying ccRCC were 74.4% and 83.9%, respectively. The sensitivity and specificity of CD10 for identifying CCOC were 93.3% and 80.6%, respectively. The combined SR-B1( +) CD10( +) immunoprofile supports the diagnosis of ccRCC with a specificity of 93.5%. The combined SR-B1(-) CD10(-) immunoprofile supports the diagnosis of CCOC with a specificity of 93.3%. CONCLUSIONS: our findings demonstrate that the combination of SR-B1 and CD10 immunoprofiling is a valuable tool for differential diagnosis of ccRCC and CCOC.

Peritoneal cavernous hemangiomatosis: A case report.

BACKGROUND: Cavernous hemangiomatosis in the liver and spleen has been reported, but it occurs less commonly in the peritoneum. Here we report a case of peritoneal cavernous hemangiomatosis and share some valuable information about this disease. CASE SUMMARY: A 57-year-old Chinese man had a huge abdominal mass with abdominal distention and a significant reduction of food consumption. An enhanced abdominal and pelvic computed tomography and positron emission tomography-computed tomography revealed multiple cystic masses on the peritoneum, greater omentum, small intestinal mesentery and the surface of the spleen, and a high maximum standardized uptake value of the largest cystic lesion. Exploratory laparotomy was performed, and multiple cystic masses were found on the surface of the peritoneum, greater omentum, mesentery of the small intestine, and surface of the liver and spleen. Dark red bloody cystic fluid was present in the cystic tumor. Pathological examination showed that in the stromal components, the irregular vascular wall was thin. The vessel lumen was interlinked, and the lumen was lined with flat endothelium. According to the intraoperative findings and pathologic results, the patient was diagnosed with peritoneal cavernous hemangiomatosis. CONCLUSION: The possibility of peritoneal cavernous hemangiomatosis should be considered when multiple cystic masses are found in the abdominal cavity by preoperative examination.

X-chromosomal inactivation analysis of uterine leiomyomas reveals a common clonal origin of different tumor nodules in some multiple leiomyomas.

Uterine leiomyomas were shown to be clonal lesions, but the relationship among different tumor nodules in multiple uterine leiomyomas remains unresolved. In this study, X-chromosomal inactivation patterns of these tumor nodules were shown by allelic polymorphism analysis through polymerase-chain reaction at the phosphoglycerate kinase and androgen receptor loci following pretreatment with the methylation-sensitive restriction enzyme HpaII or HhaI. A total number of 113 cases of uterine leiomyomas were examined. Monoclonality was demonstrated in all of the 315 nodules from 76 informative cases. The inter-nodular relationship was evaluated in 55 multiple cases with 294 tumor nodules. Different inactivation patterns were observed in 20 cases, demonstrating a multicentric origin, while an identical inactivated allele was found in all or most of the nodules in the rest of the cases, indicating a common clonal origin. The occurrence of the unicentric cases appeared to be associated with an elevated mitotic activity. Seven nodules from a multinodular case with a morphology indicative of mitotically active leiomyoma were shown to carry the identical inactivated allele, which demonstrates their unicellular origin and malignant nature. In addition, the same androgen receptor gene alteration was identified in two discrete leiomyoma nodules from a uterus. These results approve the monoclonality of uterine leiomyomas and demonstrate the presence of unicentric multiple leiomyomas.

[Retrospective analysis of three cases of pulmonary mucormycosis].

OBJECTIVE: To describe the clinical characteristics of pulmonary mucormycosis and to evaluate the approaches to its diagnosis and treatment. METHODS: Three cases of pulmonary mucormycosis were successfully diagnosed by histopathologic examination of infected tissues obtained by fiberoptic bronchoscopy in this hospital. The clinical features of the cases were analyzed and the literature reviewed. RESULTS: Three patients were all farmers and two of them had had diabetic ketoacidosis. The first patient died from massive hemoptysis one day after the diagnosis was confirmed. The second patient was cured by large doses of intravenous amphotericin B (total dosage 2 g). The third patient presented with right middle bronchial stenosis after right upper lobectomy because of squamous carcinoma, and was cured by amphotericin B (1.5 g) combined with interventional therapy under fiberoptic bronchoscopy. The two patients were followed for 0.5 - 1 year without relapse. CONCLUSIONS: The mortality of pulmonary mucormycosis is high. Fiberoptic bronchoscopy is a useful diagnostic method for histopathologic examination. Successful treatment of pulmonary mucormycosis includes early diagnosis, control of underlying diseases and surgical intervention of isolated lesions combined with large dosage of amphotericin B.

Diagnostic value of medical thoracoscopy in malignant pleural effusion induced by non-Hodgkin's lymphoma.

Malignant pleural effusion (MPE) appears in up to 20% of patients with non-Hodgkin's lymphoma (NHL). The present study aimed to assess the efficacy of medical thoracoscopy (MT) in the diagnosis of patients with MPE induced by NHL. Between July 2005 and June 2014, 833 patients with pleural effusions of unknown etiology underwent MT in Beijing Chaoyang Hospital (Beijing, China), where diagnostic thoracocentesis or/and blind pleural biopsy had failed to yield an answer. Demographic, radiographic, thoracoscopic, histological and immunophenotyping data of 10 NHL patients with MPE were then retrospectively analyzed. Under medical thoracoscopy, pleural nodules (in n=6 patients), hyperemia (n=5), plaque-like lesions (n=4), pleural thickening (n=3), cellulose (n=3), ulcer (n=2), adhesion (n=2), and scattered hemorrhagic spots (n=1) were observed on the surface of parietal pleura. Histopathological and immunohistochemical analysis of pleural biopsy samples led to a correct diagnosis of B-cell NHL in 7 patients and T-lymphoblastic NHL in 2 patients. Data from the present study demonstrated that pleural biopsy through MT achieved a definite diagnosis of NHL in 9 out of 10 (90%) patients with MPE induced by NHL. Therefore, MT is a useful method for diagnosing MPE induced by NHL.

Primary pulmonary angiosarcoma: Three case reports and literature review.

Primary pulmonary angiosarcoma is a rare type of malignant vascular tumor with a very aggressive clinical course and a grim prognosis. To date, only a handful of cases have been reported in English literature. Its rarity and consequent low index of suspicion makes clinical diagnosis difficult. In this report we present three cases of primary pulmonary angiosarcoma with cough, hemoptysis, and progressive dyspnea to contribute to the sparse literature on this disease. A review is made of previous reports of primary pulmonary angiosarcomas, and the clinical characteristics, diagnosed method, treatment options, and prognosis of pulmonary angiosarcoma are also discussed.

Epidemiology and genotype distribution of high risk human papillomavirus in population of hospital opportunistic screening.

This study aimed to determine the prevalence of high-risk human papillomavirus (HR-HPV) in population of hospital opportunistic screening and to identify the correlation of prevalent genotypes and cervical cytological abnormalities. A cross-sectional study was employed between July 2013 and July 2014 in the Chaoyang hospital, in Beijing. Cervical samples were collected for the Type-specific HPV and the cervical cytological analyses in the population of hospital opportunistic screening. Total of 8975 samples from female patients aged 17-86 years were tested. Of these, 10.4% were infected by HR-HPV, the highest prevalence of HR-HPV in the youngest group and decreasing with aging (X(2)=19.68, P=0.02). Of these, 78.73% were single infections and 21.27% were multiple infections. Age-specific prevalence of multiple HPV exhibited a "U" shaped curve (X(2)=19.98, P=0.018). The most prevalent genotype is HPV 52, then descending order of frequency were HPV-58, 16, 39, 51, 56, 59, 18, 31, 33, 35, 68 and 45. 15.9% had an abnormal cytology in HR-HPV positive women, vs 4.13% in HR-HPV negative women. The prevalence of HR-HPV were 9.2%, 26.8%, 32%, 35.3% and 36.4% in normal cell, ASCUS, LSIL, ASC-H and HSIL, respectively (X(2)=234.67, P=0.000). Women with HPV 52, 16, 18, 58, 39, 51, 59, 56, 33, 31 infections related to the abnormal cytology, while the HPV68, 45, 35 didn't. The prevalent characteristic in population of the hospital opportunistic screening is similar to the population of cervical screen, But the most five prevalent genotype in rank are different .Women with HR-HPV infections were more likely to have the cervical abnormal cytology.

[X-chromosome inactivation patterns of different tumor nodules in multiple leiomyomas of uterus].

OBJECTIVE: To describe the relationship among different tumor nodules in multiple leiomyomas of uterus. METHODS: Genomic DNA was extracted from fresh tissue samples, digested through incubation with methylation-sensitive Hha I or Hpa II, and amplified via PCR for androgen receptor (AR) and phosphoglycerate kinase (PGK) genes. The length polymorphism on AR gene was demonstrated by denaturing polyacrylamide gel electrophoresis and silver staining, the PGK gene products were treated with Bst XI and resolved on agarose gels. RESULTS: 112 cases of leiomyomas and one case of leiomyosarcoma were examined, 89% showing the length polymorphism for AR gene and 30% carrying the polymorphic Bst XI site at PGK locus. Loss of X-chromosome inactivation mosaicism was observed in all the 321 tumor nodules examined from 77 cases, reflecting their clonal cellular composition. The relationship between different nodules was evaluated by their X-chromosome inactivation patterns in the 295 tumor nodules taken from 57 multiple leiomyomas. Similar inactivated alleles were found in all nodules in 30, in most nodules in 7 cases, similar to a multi-nodular leiomyosarcoma, while 20 cases showed near-random distribution of the inactivated alleles in different nodules, indicating their multicentric origins. No relevance was found between this difference and any histopathological parameters including number of mitotic figures and occurrence of bizarre nuclei and degeneration. In addition, an identical mutation and loss of heterozygosity were found at the AR locus in two apparently discrete tumor nodules in one case, providing further evidence for the unicellular origin of these lesions. CONCLUSIONS: The multi-nodular leiomyomas may be classified into multicentric, unicentric types, as well as a mixed type. It remains to be clarified whether different nodules in the unicentric cases originate from a parent tumor by migration or by spreading.

Evaluation of ALK rearrangement in Chinese non-small cell lung cancer using FISH, immunohistochemistry, and real-time quantitative RT- PCR on paraffin-embedded tissues.

Patients with ALK gene rearrangements often manifest dramatic responses to crizotinib, an ALK inhibitor. Accurate identification of patients with ALK-positive non-small cell lung cancer (NSCLC) is essential for the clinical application of ALK-targeted therapy. However, assessing EML4-ALK rearrangement in NSCLC remains challenging in routine pathology practice. The aim of this study was to compare the diagnostic accuracy of FISH, immunohistochemistry (IHC), and real-time quantitative RT-PCR (QPCR) methodologies for detection of EML4-ALK rearrangement in NSCLC and to appraise immunohistochemistry as a pre-screening tool. In this study, a total of 473 paraffin-embedded NSCLC samples from surgical resections and biopsies were analyzed by IHC with ALK antibody. ALK rearrangement was further confirmed by FISH and QPCR. ALK protein expression was detected in twenty patients (20/473, 4.2%). Of the 20 ALK-positive cases by IHC, 15 cases were further confirmed as ALK rearrangement by FISH, and 5 cases were not interpretable. Also, we evaluated 13 out of the 20 IHC-positive tissues by QPCR in additional to FISH, and found that 9 cases were positive and 2 cases were equivocal, whereas 2 cases were negative although they were positive by both IHC and FISH. The ALK status was concordant in 5 out of 8 cases that were interpretable by three methods. Additionally, none of the 110 IHC-negative cases with adenocarcinoma histology showed ALK rearrangements by FISH. Histologically, almost all the ALK-rearranged cases were adenocarcinoma, except that one case was sarcomatoid carcinoma. A solid signet-ring cell pattern or mucinous cribriform pattern was presented at least focally in all ALK-positive tumors. In conclusion, our findings suggested that ALK rearrangement was associated with ALK protein expression. The conventional IHC assay is a valuable tool for the pre-screening of patients with ALK rearrangement in clinical practice and a combination of FISH and QPCR is required for further confirmation.

CAG repeats in the androgen receptor gene are shorter in patients with pulmonary, esophageal or bladder carcinoma and longer in women with uterine leiomyoma.

Preferential occurrence of pulmonary, esophageal and bladder carcinomas in males indicate a possible involvement of androgen receptor (AR)-mediated functions. We evaluated the roles of the CAG repeat polymorphism in AR exon 1 in development of these lesions. The exon 1 of AR gene was amplified in samples from 198 male patients with lung carcinoma, 183 with esophageal carcinoma, 95 with bladder carcinoma and 94 males with appendicitis, as a reference group. Mean numbers of the CAG repeat in these 3 cancer groups were determined to be 20.2, 20.0 and 20.0, respectively, all being significantly smaller than that of the reference group (21.1; P<0.05). Samples from 118 female patients with lung carcinoma and 154 females with appendicitis, as a reference group, were examined, with the mean CAG repeat number significantly smaller (19.8) than that of the female reference group (20.7; P<0.01). Samples from 108 patients with uterine leiomyoma were also examined, and their CAG repeat numbers were found to be markedly expanded (23.4; P<0.01). The patients with multiple leiomyomas tend to carry a longer CAG repeat structure, with the mean CAG repeat number longer in the multicentric multiple cases (24.1) compared to that of the unicentric, multinodular cases (22.2) and those with solitary lesions (23.1; P<0.01). These results indicate that a shorter CAG repeat structure may predispose individuals to a higher risk to some male-predominant neoplasms including pulmonary, esophageal and bladder carcinomas and a longer one confers women greater susceptibility to leiomyoma development in the uterus.