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Intestinal metaplasia (IM) in the esophagus is considered as a risk factor of subsequent intestinal-type adenocarcinoma based on the classical theory of metaplasia-dysplasia-carcinoma. IM rarely occurs in urinary tract and fewer studies have been reported with long-term follow-up in those patients with IM of bladder. Thus, the etiology, pathological characteristics and prognosis of IM of urinary tract remain unclear. In the past, IM was regarded as benign lesions in bladder and there might have no relationship between IM of bladder and potential malignancy. Recently, some studies suggested that IM of bladder might indicate a risk of progression to carcinoma and require active surveillance according to their findings. However, due to limited cases, there has not yet been any systematic review or consensus on the management of IM of bladder. Here we reported a patient diagnosed as pulmonary intestinal adenocarcinoma suspiciously secondary to IM of bladder, without primary gastrointestinal cancer or bladder adenocarcinoma. Receiving lung surgery and adjuvant chemotherapy, the patient had no recurrence after a follow-up of 27 months. Hence, the present case demonstrated that ectopic IM can be a driving factor of adenocarcinoma in other organs, such as pulmonary intestinal adenocarcinoma, and it requires a long-term follow-up with overall examinations.

Adenocarcinoma of the bladder (ACB) rarely occurs but is associated with poor outcome. We aim to establish reliable nomograms for estimating cancer-specific survival (CSS) and overall survival (OS) of ACB patients.ACB patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015). A total of 1,149 patients were randomly divided into training cohort (OS nomogram incorporated age, race, histologic grade, American Joint Committee of Cancer (AJCC) stage, metastasis, surgery, chemotherapy, and tumor size. The C-indices were 0.754 (95% CI: 0.732-0.775) for training set and 0.743 (95% CI: 0.712-0.767) for validation set. Meanwhile, the calibration plots for 3- and 5-year OS displayed fine concordance between actual and predicted outcomes. In addition, higher areas under the curve (AUCs) were seen in training cohort (3-year: 0.799 vs. 0.630; 5-year: 0.797 vs. 0.648) and validation cohort (3-year: 0.802 vs. 0.662; 5-year: 0.752 vs. 0.660). Finally, DCA curves of the nomograms exhibited larger net benefits than AJCC stage. CSS nomogram showed similar results.Our study constructed and validated nomograms with improved discriminative abilities and clinical benefits to predict the survival outcomes of ACB patients. The models might assist clinicians in optimizing therapeutic management on individual levels.

Background The new subtypes of lung adenocarcinoma reflect local invasive growth, pulmonary alveoli, and intraluminal spreading, while the effective improvement of the diagnostic yield of bronchoscopy still remains unclear. This study aims to explore whether the subtypes of lung adenocarcinoma and other factors affect the diagnostic yield of bronchoscopy. Methods All patients were performed 64-row CT examination and bronchoscopy. Results The bronchus cutoff sign in 48 cases and the endoscopic diagnostic yield was 60.4%. The lumen of the lobes and segments was invaded in 59 cases, and the endoscopic diagnostic yield was 54.2%.The lymph node metastasis was detected in 46 cases, and the endoscopic diagnostic yield was 60.9%. In addition, 42 cases showed acinar type-predominant, and the endoscopic diagnostic yield was 28.6%. Eighteen cases showed solid type-predominant, and the endoscopic diagnostic yield was 33.3%. The micropapillary type-predominant was noted in 17 cases, with the endoscopic diagnostic yield as 94.1%. The papillary type-predominant was in 14 cases, and the endoscopic diagnostic yield was 42.9%. The lepidic type-predominant was seen in 13 cases, and the endoscopic diagnostic yield was 7.7%. The mean diameter of tumors with a positive endoscopic diagnostic yield was 4.34±2.65cm, and the mean diameter of tumors with a negative diagnostic yield was 2.83±1.47cm. Multivariate analysis showed that micropapillary lung adenocarcinoma affected the endoscopic diagnostic yield (OR=37.594, 95% CI: 4.074-346.94) .Tumor diameter affects endoscopic diagnostic yield (OR=1.39, 95% CI: 1.073-1.802), bronchus cutoff sign is easy to obtain endoscopic diagnostic yield (OR=4.86, 95% CI: 1.606-14.704), and lymph node metastasis affects the endoscopic diagnostic yield (OR=3.696, 95% CI: 1.255-10.883). Conclusion The micropapillary subtype lung adenocarcinoma has a certain influence on the diagnostic yield of bronchoscopy. When the lung adenocarcinoma has a large tumor diameter, bronchus cutoff sign and lymph node metastasis, it is easy to obtain a diagnostic yield of bronchoscopy.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor with rapid progression and poor prognosis. In the present study, 11 high‑quality microarray datasets, comprising 334 tumor samples and 151 non‑tumor samples from the Gene Expression Omnibus, were screened, and integrative meta‑analysis of expression data was used to identify gene signatures that differentiate between PDAC and normal pancreatic tissues. Following the identification of differentially expressed genes (DEGs), two‑way hierarchical clustering analysis was performed for all DEGs using the gplots package in R software. Hub genes were then determined through protein‑protein interaction network analysis using NetworkAnalyst. In addition, functional annotation and pathway enrichment analyses of all DEGs were conducted in the Database for Annotation, Visualization, and Integrated Discovery. The expression levels and Kaplan‑Meier analysis of the top 10 upregulated and downregulated genes were verified in The Cancer Genome Atlas. A total of 1,587 DEGs, including 1,004 upregulated and 583 downregulated genes, were obtained by comparing PDAC with normal tissues. Of these, hematological and neurological expressed 1, integrin subunit α2 (ITGA2) and S100 calcium‑binding protein A6 (S100A6) were the top upregulated genes, and kinesin family member 1A, Dymeclin and β‑secretase 1 were the top downregulated genes. Reverse transcription‑quantitative PCR was performed to examine the expression levels of S100A6, KRT19 and GNG7, and the results suggested that S100A6 was significantly upregulated in PDAC compared with normal pancreatic tissues. ITGA2 overexpression was significantly associated with shorter overall survival times, whereas family with sequence similarity 46 member C overexpression was strongly associated with longer overall survival times. In addition, network‑based meta‑analysis confirmed growth factor receptor‑bound protein 2 and histone deacetylase 5 as pivotal hub genes in PDAC compared with normal tissue. In conclusion, the results of the present meta‑analysis identified PDAC‑related gene signatures, providing new perspectives and potential targets for PDAC diagnosis and treatment.

Yunqiang Nie,1 Hongjun Liu,2 Xiao Tan,3 Hui Wang,1 Fuzhou Li,4 Cuiyun Li,1 Ping Han,1 Xin Lyv,1 Xinyi Xu,1 Miao Guo5 1Department of Respiratory Medicine, Linyi People’s Hospital, Linyi 276000, China; 2Department of Internal Medicine, 120 Emergency Command Center of Linyi City, Linyi 276002, China; 3Department of Pathology, Linyi People’s Hospital, Linyi 276000, China; 4Department of Radiology, Linyi People’s Hospital, Linyi 276000, China; 5Department of Geriatrics, Linyi People’s Hospital, Linyi 276000, China Background: The aim of this study was to investigate the correlation of EGFR mutation on the high-resolution computed tomography (HRCT) features in lung adenocarcinoma. Patients and methods: A total of 121 patients were diagnosed with lung adenocarcinoma from January 2014 to December 2016. The correlation of indexes (gender, age, tumor diameter, and EGFR mutation) was analyzed based on the HRCT characteristics of lung adenocarcinoma. Results: There were 73 cases of EGFR mutation and 48 cases of wild-type EGFR. One hundred and three cases had pleural indentation that was significant in patients with EGFR mutation than those with wild-type EGFR (P=0.038). Forty-two out of 121 cases exhibited the bronchus cutoff sign. Patients with EGFR mutation were likely to develop the bronchus cutoff sign (P=0.017). Sixty-one out of 121 cases exhibited the lobulation sign, which was significant in patients with EGFR mutation than those with wild-type EGFR (P0.05). Age and gender did not vary significantly in the lobulation sign (P>0.05). Conclusion: HRCT characteristics such as pleural indentation, bronchus cutoff sign, and lobulation sign in lung adenocarcinoma with EGFR mutation were significantly greater than those with wild-type EGFR; however, further study is essential in determining the predictive ability of computed tomography (CT) for EGFR mutations in lung adenocarcinoma. Keywords: computed tomography, EGFR mutation, lung adenocarcinoma, pleural traction, bronchus cutoff sign

Objective To investigate current status of diagnosis and treatment of bladder cancer in China. Methods A database was generated by Chinese Bladder Cancer Consortium (CBCC). From January 2007 to December 2012, 14,260 cases from 44 CBCC centers were included. Data of diagnosis, treatment and pathology were collected. Results The average age was 63.5 year-old and most patients were male (84.3%). The most common histologic types were urothelial carcinoma (91.4%), adenocarcinoma (1.8%), and squamous carcinoma (1.9%). According to 1973 and 2004 WHO grading system, 42.0%, 41.0%, and 17.0% of patients were grade 1, 2, and 3, and 16.0%, 48.7%, and 35.3% of patients were papillary urothelial neoplasms of low malignant potential, low, and high grade, respectively. Non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) were 25.2% and 74.1%, respectively (0.8% not clear). Carcinoma in situ was only 2.4%. Most patients were diagnosed by white-light cystoscopy with biopsy (74.3%). Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%, respectively. Diagnostic transurethral resection (TUR) provided detection rate of 16.9%. Most NMIBCs were treated with TUR (89.2%). After initial TUR, 2.6% accepted second TUR, and 45.7%, 69.9%, and 58.7% accepted immediate, induced, and maintenance chemotherapy instillation, respectively. Most MIBCs were treated with radical cystectomy (RC, 59.7%). Laparoscopic RCs were 35.1%, while open RC 63.4%. Extended and standard pelvic lymph node dissection were 7% and 66%, respectively. Three most common urinary diversions were orthotopic neobladder (44%), ileal conduit (31%), and ureterocutaneostomy (23%). Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18% of T3 and T4 patients accepted adjuvant chemotherapy. Conclusion Disease characteristics are similar to international reports, while differences of diagnosis and treatment exist. This study can provide evidences for revisions of the guideline on bladder cancer in China.

Background Total pancreatectomy (TP) is an operation that has long been associated with high morbidity and mortality, and rarely advocated for treatment of pancreatic tumours. Because of the improvements in diabetes management, there has been renewed interest in TP for treatment of pancreatic neoplasm, with a need to reassess outcomes. Methods Fifteen patients (9%) underwent TP in a single Australian high-volume tertiary institution between August 2005 and January 2012. Pancreaticoduodenectomy (PD) was performed in 150 patients during the same time period. Indications and peri-operative outcomes of patients were compared. Results TP was performed for treatment of malignancy in 13 (87%) cases, for tumours involving the pancreatic neck. Complete tumour clearance achieved. Portal vein resections were more frequently required than in the PD group (5 (33%) versus 9 (6%); P = 0.004), as were blood transfusions (11 (73%) versus 28 (19%); P < 0.001), and median operative times were longer (10.5 versus 7.0 h; P < 0.001). Overall, complications were significantly greater in the TP group compared with the PD group (13 (87%) versus 86 (57%); P = 0.029), but the difference was mainly as a result of high grade I complications, in particular symptomatic hypoglycaemia (4 (27%) versus 0 (0%): P < 0.001) that could be easily managed. The overall lengths of stay and readmission rates were similar between groups. Conclusion TP should be considered in selective cases for treatment of pancreatic neoplasm if it allows complete clearance. The procedure does not appear to be associated with significant increases in serious complications compared with PD.

Resectable lung adenocarcinoma is dominated by peripheral distribution, and surgical resection is the main treatment protocol. However, high recurrence rate remains after surgery. Lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutation has strong invasion ability, but the effects of this mutation on local invasion in early lung adenocarcinoma have been rarely studied. This study aimed to assess the effects of EGFR mutation on local invasion in resectable lung adenocarcinoma. A retrospective analysis of 103 patients clinically diagnosed with peripheral lung adenocarcinoma was included. They underwent preoperative bronchoscopy, which indicated grades 2 or 3 bronchial involvement (lumen of the lobe or segment). The associations of EGFR mutation with pleural invasion, endobronchial metastasis, and lymph node metastasis were analyzed according to pathologies of pleural invasion and lymph node metastasis, as well as EGFR gene mutation detected by postoperative pathological specimens. Statistical analyses were performed by unpaired Chi-square test using the SPSS16.0 software. In patients with EGFR mutation, pleural invasion, endobronchial metastasis, and lymph node metastasis rates were 62.5, 39.1, and 34.4%, respectively, indicating statistically significant differences (p = 0.003). Meanwhile, the pleural invasion rate in patients with wild-type EGFR was 43.6%, significantly reduced compared with patients with mutated EGFR (62.5%; p = 0.018). In addition, the endobronchial metastasis rate in patients with wild-type EGFR was 17.9%, significantly lower than in patients with EGFR mutation (39.1%; p = 0.005). However, lymph node metastasis rates were similar between EGFR mutated and wild-type patients (34.4 vs 25.6%, respectively, p > 0.05). Early resectable lung adenocarcinoma patients with EGFR mutation showed a higher rate of local invasion compared with those harboring wild-type EGFR. This finding provides a basis for improved therapy. This study was supported by Project of Medical and Health Science Technology in Shandong Province ( 2015WS0376 )

The choice of appropriate therapeutic plans for primary endocervical adenocarcinomas (ECA) and endometrial adenocarcinomas (EMA) depends on the tumor's site of origin. Some panels of antibodies help to distinguish primary ECA from EMA. However, unexpected expressions of those markers often exist, which causes this diagnostic dilemma to be still unresolved. In this study, we investigate five commonly used monoclonal antibodies (p53, TTF1, CK7, CK20, and CK34betaE12) to evaluate their potential use in distinguishing between these two gynecologic malignancies.A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 35 hysterectomy specimens, including 14 ECA and 21 EMA. Utilizing the avidin-biotin (ABC) technique, tissue array sections were immunostained with the five aforementioned commercially available antibodies.Immunohistochemical (IHC) expressions of p53, TTF1, CK7, CK20, and CK34betaE12 were all nonsignificant (P0.05) in frequency differences between the immunostaining results (positive vs. negative) in tumors from both the two primary adenocarcinomas (ECA vs. EMA).It is still uncertain which markers or panels would be the most appropriate for making diagnoses; hence, exploration of other useful markers, which make a definitive distinction between ECA and EMA merits further studies. This study, however, uncovered that the five commonly used monoclonal antibodies (p53, TTF1, CK7, CK20, and CK34betaE12) are of no beneficial value in distinguishing between primary ECA and EMA.

Endocervical adenocarcinomas (ECAs) and endometrial adenocarcinomas (EMAs) are malignancies that affect the uterus; however, their biological behaviors are quite different. This distinction has clinical significance because the appropriate therapy may depend on the site of tumor origin. The purpose of this study is to evaluate two different scoring mechanisms of p16INK4a immunohistochemical (IHC) stain in distinguishing between primary ECAs and EMAs. A tissue microarray (TMA) was constructed using formalin-fixed, paraffin-embedded tissue from hysterectomy specimens, including 14 ECAs and 21 EMAs. Tissue array sections were stained with a commercially available antibody, p16INK4a. The avidin–biotin complex method was used to visualize antigens. The staining intensity and extent of the IHC reactions were evaluated using a semi-quantitative scoring system. Two scoring methods were defined on the following bases: (1) independent cytoplasmic staining alone, irrespective of nucleic stain (Method C) and (2) independent nucleic staining alone, irrespective of cytoplasmic staining. (Method N). Of the two scoring mechanisms for p16INK4a expression, Method N showed a significant difference (P = 0.015), but Method C showed no significant (P = 0.432) frequency differences in distinguishing between ECAs and EMAs. However, Method N had a higher overall accuracy rate (71.4%) in accurately diagnosing ECAs from EMAs in the total number of p16INK4a IHC cases. According to the data of p16INK4a expression in this TMA study, Method N is favorable and efficient in distinguishing between ECAs and EMAs, while Method C is not.

Pancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers and it is insensitive to many chemotherapeutic drugs. The molecular basis of pancreatic cancer remains to be elucidated. Investigations into the molecular mechanism involved in the development and progression as well as drug resistance of the disease may be useful to understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In the present study, we showed that salt-inducible kinase 1 (SIK1) was downregulated and loss of SIK1 was associated with gemcitabine resistance in pancreatic cancer. In pancreatic cancer cells, SIK1 inhibited proliferation, migration and invasion. An analysis of potential microRNA target sites was performed using the prediction algorithms, miRanda, TargetScan and PicTar. The three algorithms predicted that miR-203 is capable of targeting 3'UTR of SIK1. Subsequent experiments confirmed the prediction. In addition, the results showed that miR-203 promotes proliferation, migration and invasion in pancreatic cancer cells, whereas the restoration of SIK1 abrogated the regulation of pre-miR‑203-mediated proliferation, migration and invasion.

Hepatoid carcinoma is a unique type of extrahepatic tumor associated with hepatic differentiation and displays the morphological and functional features of hepatocellular carcinoma. Hepatoid carcinoma of the extrahepatic duct has rarely been reported in the literature. We report a 62-year-old man who presented with epigastric discomfort, xanthochromia, dull pain of the right shoulder, nausea and pruitus. Microscopic examination of the extrahepatic duct indicated that the tumor was primarily composed of “hepatoid cells”, which were characterized by an eosinophilic cytoplasm, enlarged nucleus and prominent nucleoli. The cells were arranged in nests or proliferated in a trabecular pattern. Immunohistochemistry indicated that the tumor cells were positive for hepatocyte paraffin 1 and cytokeratins 8 and 18. Based on these findings, this case was diagnosed as hepatoid carcinoma of the extrahepatic duct.

to investigate the chromosomal characteristics of pancreatic ductal adenocarcinomas by spectral karyotyping.cytogenetic aberrations of pancreatic cancer cell line P2 established from a Chinese patient was investigated by spectral karyotyping (SKY). Chromosomal alterations were further evaluated in 10 cases of pancreatic cancer and 10 cases of chronic pancreatitis by two color fluorescence in situ hybridization (FISH) by using EGFR/CEP7 probe and paraffin embedded tissue samples.hypotriploid and 26 chromosomal aberrations were revealed in cell line P2. Recurrent chromosomal numerical alterations included loss of chromosome 4, 9, 18, 19, 22, Y, 10p, 15p, 8p, 6q and 12p, with gain of chromosome 7 and 12q. Frequent chromosomal structural abnormalities included der(9;15)(q10;q10), der(10)(3;10)(?;q26) and der(12)(8;12)(?;p13). Four of 10 cases showed EGFR copy number changes by FISH.highly complex chromosomal rearrangements occur in pancreatic cancers. Additional studies of more cases are needed, including FISH analysis of EGFR copy number changes, to reach a conclusion.

The choice of appropriate therapeutic plans for primary endocervical adenocarcinomas and endometrial adenocarcinomas depends on the site of origin of the tumor. The purpose of this study was to make clear whether the immunohistochemistry of the true cytokeratin 8/18 monoclonal antibody (Leica Microsystems, Newcastle, United Kingdom), instead of CAM 5.2 (Becton Dickinson Biosciences, San Jose, CA), has potential use in distinguishing between endocervical adenocarcinomas and endometrial adenocarcinomas. A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 34 hysterectomy specimens, including 14 endocervical adenocarcinomas and 20 endometrial adenocarcinomas. Using the Bond-Max autostainer (Leica Microsystems) and the associated Bond Refine Polymer Detection Kit, tissue array sections were immunostained with cytokeratin 8, 18, and 8/18 commercially available antibodies. The immunohistochemical expressions of all 3 markers, cytokeratin 8, 18, and 8/18 showed nonsignificant (P>0.05) frequency differences between the immunostaining results (positive vs. negative) in tumors of both gynecologic adenocarcinomas. Although CAM 5.2 has been reported to be helpful in distinguishing between primary endocervical adenocarcinomas and endometrial adenocarcinomas, we could not verify this point of view using the true cytokeratin 8/18 monoclonal antibody (Leica Microsystems). It has often been mistakenly cited that CAM 5.2 reacts with cytokeratin 8 and 18, and the results herein confer that there is a wrong impression that cytokeratin 8/18 is differentially expressed in these 2 gynecologic malignancies. In conclusion, the true cytokeratin 8/18 monoclonal antibody is of no use in distinguishing between primary endocervical adenocarcinomas and endometrial adenocarcinomas.

Gynecological pathologists are used to operating many panels of various markers in combination for the diagnostic distinction between primary endocervical and endometrial adenocarcinomas. The conventional 3-marker (ER/Vim/CEA) panel is the most promising tool. In this study, our aim is to investigate whether a 2-marker panel is enough to distinguish between these two gynecologic malignancies. Additionally, we wish to determine which one is the most favorable among eight panels tested, including six 2-marker (ER/CEA, PR/CEA, Vim/CEA, ER/p16(INK4a), PR/p16(INK4a), Vim/p16(INK4a)) and two 3-marker (ER/Vim/CEA, ER/Vim/p16(INK)) panels. A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 35 hysterectomy specimens, including 14 primary endocervical adenocarcinomas and 21 primary endometrial adenocarcinomas. Utilizing the avidin-biotin complex (ABC) method, tissue array sections were immunostained with five commercially available antibodies (ER, Vim, CEA, PR, and p16(INK4a)) to evaluate their individual frequencies of expression. We found that all eight aforementioned panels showed an encouraging range of overall accuracy (69.2% to 78.3%). However, one panel of 2-markers (Vim, CEA) exhibited the most efficiency (78.3%) in the diagnostic distinction between primary endocervical and endometrial adenocarcinomas. Based on the analyzed data, we conclude that the 2-marker (Vim/CEA) panel seems adequate to be an appropriate, convenient, and efficient means to distinguish between primary endocervical and endometrial adenocarcinomas. Even though there were a limited number of cases, this study still provides valuable references to help avoid wasting resources and unnecessary marker testing.

Endocervical adenocarcinomas (ECAs) and endometrial adenocarcinomas (EMAs) are malignancies that affect the uterus; however, their biologic behaviors are quite different. This distinction has clinical significance, because the appropriate therapy may depend on the site of tumor origin. In this study, we not only compare the individual expression status of 4 immunomarkers [estrogen receptor (ER), vimentin (Vim), carcinoembryonic antigen (CEA), and p16 INK4a ], but also evaluate whether p16 INV4a adds value to the ER/Vim/CEA panel characteristics and performance in distinguishing between primary ECA and EMA. A tissue microarray (TMA) was constructed using paraffin-embedded, formalin-fixed tissues from 38 hysterectomy specimens, including 14 ECAs and 24 EMAs. Tissue microarray sections were immunostained with 4 antibodies, by the avidin-biotin complex method for antigen visualization. The staining intensity and area extent of the immunohistochemical reactions were evaluated using the semiquantitative scoring system. The 3 markers (ER, Vim, CEA) and their respective panel expressions showed statistically significant (P

The accurate distinction between primary endocervical adenocarcinomas (ECA) and endometrial adenocarcinomas (EMA) may require the use of multiple ancillary monoclonal antibodies in panels of immunohistochemistry stains. In addition to reappraising the expressions of four commonly used individual monoclonal antibodies [estrogen receptor (ER), Vimentin (Vim), carcinoembryonic antigen (CEA), and p16(INK4)], this study was designed to investigate whether CEA and p16(INK4) can be effectively exchanged between two relevant three-marker panels (ER/Vim/CEA vs. ER/Vim/p16(INK4)) in distinguishing ECA from EMA. A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 35 hysterectomy specimens, including 14 ECA and 21 EMA. Utilizing the avidin-biotin technique, tissue array sections were immunostained with the four aforementioned individual markers (ER, Vim, CEA, and p16(INK4)). In addition to the four individual monoclonal antibodies, both their respective three-marker panels, proposed here, showed statistically significant (p0.05) frequency differences between these two gynecologic tumors (ECA vs. EMA). The panel performance and test effectiveness revealed that both three-marker panels are promising and very helpful. According to our data, when histomorphological and clinical doubt exists as to the primary site of origin, we recommend using either of these two conventional three-marker panels, which consist of ER/Vim/CEA and ER/Vim/p16(INK4). CEA and p16(INK4) can be interchanged with confidence without significantly influencing the panel presentations and efficiencies in distinguishing between adenocarcinomas of endocervical and endometrial origin.

Endocervical adenocarcinomas and endometrial adenocarcinomas are malignancies that affect uterus; however, their biological behaviors are quite different. This distinction has clinical significance, because the appropriate therapy may depend on the site of tumor origin. The purpose of this study is to evaluate four different scoring methods of p16(INK4a) immunohistochemical staining in distinguishing between primary endocervical adenocarcinomas and endometrial adenocarcinomas from limited sizes of tissue specimens. A tissue microarray was constructed using formalin-fixed, paraffin-embedded tissue from hysterectomy specimens, including 14 endocervical adenocarcinomas and 21 endometrial adenocarcinomas. Tissue array sections were immunostained with a commercially available antibody of p16(INK4a). Avidin-biotin complex method was used for antigens visualization. The staining intensity and area extent of the immunohistochemistry was evaluated using the semiquantitative scoring system. Of the four scoring methods for p16(INK4a) expression, Method Nucleus, Method Dominant Cytoplasm or Nucleus, and Method Mean of Cytoplasm plus Nucleus showed significant (P values

The choice of appropriate therapeutic plans for primary endocervical adenocarcinomas (ECA) and endometrial adenocarcinomas (EMA) depend on the tumor's site of origin. The purpose of this study was to compare the performances of the commonly used three-marker (ER/Vim/CEA), four-marker (ER/Vim/CEA/PR) and five-marker (ER/Vim/CEA/PR/p16INK4a) panels in distinguishing between primary ECA and EMA.A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 35 hysterectomy specimens, including 14 ECA and 21 EMA. Utilizing the avidin-biotin (ABC) technique, tissue array sections were immunostained with five commercially available antibodies (ER, Vim, CEA, PR and p16INK4a) to evaluate the performances of their respective three-, four- and five-marker panels in distinguishing between primary ECA and EMA.ER, PR and Vim were more likely to be expressed in EMA, while CEA and p16INK4a were frequently expressed in ECA. The three-marker (ER/Vim/CEA) panel exhibits the most favorable performance in the distinction between these two gynecologic malignancies (ECA vs. EMA).According to our data, when histomorphological and clinical doubt exists as to the primary site of origin, we recommend that the conventional three-marker (ER/Vim/CEA) panel is sufficient, appropriate and useful in distinguishing between primary ECA and EMA, instead of the four-marker (ER/Vim/CEA/PR) and five-marker (ER/Vim/CEA/PR/p16INK4a) panels. Ancillary PR and p16INK4a add no supplementary value to the performance of the conventional three-marker (ER/Vim/CEA) panel.

Endocervical adenocarcinomas (ECA) and endometrial adenocarcinomas (EMA) are uterine malignancies that have differing biological behavior. The choice of appropriate therapeutic plan depends indeed on the tumor’s site of origin. In this study, we not only compare the individual expression status of five immunomarkers (ER, PR, Vim, CEA, and p16INK4a), but also evaluate whether p16INK4a adds value to the ER/PR/Vim/CEA panel characteristics in distinguishing between primary ECA and EMA. A tissue microarray (TMA) was constructed using paraffin-embedded, formalin-fixed tissues from 35 hysterectomy specimens, including 14 ECA and 21 EMA. TMA sections were immunostained with five anti-bodies, by avidin–biotin complex (ABC) method for antigen visualization. The staining intensity and area extent of the immunohistochemical (IHC) reactions were appraised by using the semi-quantitative scoring system. The four respective markers (ER, PR, Vim, CEA) and their combined panel expressions showed significant (p

To study the expression of matrix metalloproteinase-2 (MMP-2) in cancer of uterine cervix and correlate its expression with clinicopathological parameters, recurrence and survival of patients.Twenty cervical cancer and 20 normal tissues from the same patients were collected to detect MMP-2 mRNA expression. From them, 16 cancer and 16 normal tissues were collected and added with another 64 cancer tissues to construct a 96-tissue core microarray for immunohistochemical study. We evaluated the relationships among MMP-2 immunoreactivity using semiquantitative H scores, obtained by multiplying proportion score of stained cells and their mean digital density, and clinicopathological variables, recurrence and survival in cervical cancer patients. We used univariate and multivariate analyses of all parameters for recurrence and survival, further including time interval for evaluation.MMP-2 mRNA expression was higher in most of cervical cancerous tissues than normal counterparts. H score of MMP-2 was significantly higher in cancerous tissue cores than normal counterparts (median H scores: 1.5 vs. 0.3, P0.001). MMP-2 expression was significantly associated with parametrium invasion (P=0.004) and lymph node metastasis (P=0.015), but not with cancer recurrence, recurrence-free and overall survival rates of these patients. However, poor tumor cell differentiation and positive parametrium invasion significantly increased the recurrence and poor cell differentiation increased the risk of death.MMP-2 is highly expressed in cervical cancer tissues at mRNA and protein levels and associated with lymph node metastasis and parametrium invasion but not predictive of recurrence and survival in cervical cancer patients.

Previously, we had reviewed 43 cases of invasive cancers, adenosquamous cell carcinoma and adenocarcinoma for HPV type infections. With the same cases we extended the investigation to cytomegalovirus (CMV) and herpes simplex virus (HSV) infections. Results show that the prevalence of CMV and HSV infections from these cases of cervical carcinoma was 67 and 76%, respectively, by polymerase chain reaction. The results of the analysis of the association of HPV, CMV and HSV with various clinical characteristics of cervical cancer patients indicated that the correlation between HSV infections and clinical stages of squamous carcinoma was marginally significant (P = 0.068). HSV infections seemed to have a higher association with cell keratinization pattern as compared with the other two viral infections.