Filaggrin and Periostin Expression Is Altered in Eosinophilic Esophagitis and Normalized With Treatment.

OBJECTIVES: Previous data have suggested that filaggrin (FLG) and periostin (POSTN) genes may be dysregulated in eosinophilic esophagitis (EoE). We aimed to further evaluate the expression patterns of FLG and POSTN proteins in esophageal tissue samples of patients with EoE, as compared to those of patients with gastroesophageal reflux disease (GERD) and normal controls. METHODS: A total of 61 prospectively collected cases, including 40 children with EoE and 21 children with GERD, and a control group of 14 sex- and age-matched healthy children were enrolled. Patients with EoE were treated with skin testing-driven elimination diet and/or corticosteroids. The immunohistochemical expression of FLG and POSTN was evaluated in esophageal biopsies obtained from patients and controls, and the results were correlated with EoE-related clinicopathological parameters. RESULTS: Positive FLG and negative POSTN staining were observed in all esophageal biopsies from normal controls. In contrast, FLG and POSTN stained negative and positive, respectively, in all pretreatment biopsies obtained from patients with EoE, whereas FLG and POSTN stained positive in 57.1% and 95.2% of GERD cases, respectively (P < 0.001). A statistically significant decrease of the proportion of cases with negative FLG and positive POSTN staining was observed from the first (pretreatment) to the second (post-treatment) biopsy in the subgroup of patients with EoE (P < 0.001 in both correlations). CONCLUSIONS: FLG and POSTN expression may be downregulated and upregulated, respectively, in the esophageal mucosa of patients with active EoE, and these changes may be restored with treatment in a significant percentage of cases.

Cytomorphometric study of epithelial cells in normal and cataractous human lenses in relation with hyperglycemia.

The aim of the study is to evaluate and correlate the morphology and cell density of epithelial cells adhering to lens capsule surgically removed from the anterior central region with lens clarity and type of cataract present in patients with or without type 2 diabetes. Capsulorhexis specimens were obtained from patients who had undergone phacoemulsification cataract surgery. All the samples were centrifuged and stained by the aid of Papanicolaou technique and were observed under light microscope. We determinated the mean cell density, the degree of epithelial damage, and morphological indicators of cells such as cell area and the nucleus-plasma ratio. Patients with cataract demonstrated a statistical significant decrease in cell density and an heterogeneous cell picture in which enlarged cells dominated. In addition, type 2 diabetics with cataract had a significantly even lower mean epithelial cell density by the presence of larger cell area with smaller nucleus-plasma ratio. More pronounced alterations in the lens epithelium were correlated not only with the presence of cortical cataract, increased fasting blood sugar, and increased HbA1c but also with the prolonged duration of diabetes and the co-existence of diabetic retinopathy. It seems that density and morphology of the anterior lens epithelial cells determine the lens epithelium damage which is more profound in hyperglycemia and in cortical cataracts. The changes in lens epithelium seem to play an important role in cataractogenesis.

Differential transcriptional and protein expression of thyroid-stimulating hormone receptor in ovarian carcinomas.

OBJECTIVE: Thyroid-stimulating hormone (TSH) regulates normal thyroid function by binding to its receptor (thyroid-stimulating hormone receptor -TSHR) that is expressed at the surface of thyroid cells. Recently, it has been demonstrated that TSHR is abundantly expressed in several tissues apart from the thyroid, among them the normal ovarian surface epithelium. The role of TSHR expression outside the thyroid is not completely understood. The current study examines possible alterations of TSHR expression in ovarian carcinomas and its implication in ovarian carcinogenesis. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction and immunohistochemistry analysis of TSHR expression were performed in 34 ovarian carcinoma specimens and 10 normal ovarian tissues (controls). RESULTS: Significant reduction in TSHR messenger RNA (mRNA) expression was detected in ovarian carcinomas (mean [SD]: 0.518 [0.0934] vs normal, 49.4985 [89.1626]; P < 0.001, Mann-Whitney U test), whereas TSHR protein levels were significantly increased (percentage of positive cells: cancer, 73.55% [20.09%], vs normal, 54.54% [21.14%]; intensity: cancer, 2.52 [0.508], vs normal 1 [0]; P = 0.012, Mann-Whitney U test). No significant differences in TSHR mRNA were found according to history of thyroid disease. CONCLUSIONS: Our study describes for the first time alterations in TSHR expression both at mRNA and protein levels in ovarian carcinomas. The discrepancy between the decreased levels of the TSHR mRNA and the increased protein expression has already been described in thyroid carcinomas and might be due to alterations in its degradation by the ubiquitin system or other unknown mechanisms. Further analysis could elucidate the role of these findings in ovarian carcinogenesis.

Immunohistochemical expression of p53, p63, c-myc, p21(WAF1/cip1) and p27(kip1) proteins in urothelial bladder carcinoma: correlation with clinicopathological parameters.

PURPOSE: To reevaluate the expression levels of p53, p63, c-myc, p21(WAF1/cip1) and p27(kip1) proteins and their potential association with standard clinicopathological parameters, including tumor stage and grade, in urothelial bladder carcinoma (UBC). METHODS: Immunohistochemistry was performed in 100 transurethral resection specimens obtained from prospectively identified patients with primary UBC. RESULTS: Overall, 26, 41 and 75% of the cases showed positive staining for p53, p63 and c-myc, respectively, while p21(WAF1/cip1) and p27(kip1) expression levels were altered in 75 and 88% of the cases, respectively. Positive staining for p53 was associated with increased tumor stage (pT2) (p=0.037), while altered expression of p27(kip1) was strongly associated with male gender (p=0.009). CONCLUSION: The results of our study imply that p53 overexpression may be a useful marker of tumor invasion in UBC. In contrast, we failed to demonstrate any statistically significant correlation between the remaining markers evaluated and tumor stage or grade.

VEGF directly suppresses activation of T cells from ovarian cancer patients and healthy individuals via VEGF receptor Type 2.

The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis is well characterized; nevertheless, it is also a key element in promoting tumor evasion of the immune system by downregulating dendritic cell maturation and thus T cell activation. We sought to investigate the possible direct effect of VEGF on T cell activation and through which type of VEGF receptor (VEGFR) it exerts this effect. Circulating T cells from healthy donors and ovarian cancer patients were expanded in cultures with anti-CD3 and IL-2 with or without VEGF for 14 days, and the number of T cells was assessed. Cultured T cells were also tested for their cytotoxic activity in a standard 4-hr (51) Cr-release assay, and the expression of VEGFRs 1, 2 and 3 was assayed by flow cytometry, immunocytochemistry and Western blotting. To assess the ability of activated T cells to secrete VEGF, levels in culture supernatants were measured by enzyme linked immunosorbent assay. The addition of VEGF in cultures significantly reduced T cell proliferation in a dose-dependent manner. Protein expression studies demonstrated that CD3(+) T cells express VEGFR-2 on their surface upon activation. Experiments with anti-VEGFR-2 antibodies showed that the direct suppressive effect of VEGF on T cell proliferation is mediated by VEGFR-2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells and that activated T cells secrete VEGF in the culture environment. Overall, our study shows that T cells secret VEGF and expresses VEGFR-2 upon activation. VEGF directly suppresses T cell activation via VEGF receptor type 2.

Exosomes on Endometrial Cancer: A Biomarkers Treasure Trove?

Endometrial cancer (EC) is one of the main causes of cancer-related death among women. In the last decade, the incidence of EC is on the rise, and the relative 5-year survival remains unchanged. This creates a dire need for new diagnostic and therapeutic approaches that can only result from a deeper understanding of the pathogenesis of the disease. In this direction, exosomes are under heavy research, with two main aims: to identify the potential diagnostic and prognostic markers and to develop technologies based on their use as therapeutic vectors targeting EC cells. Exosomes are widely available in all bodily fluids and are sources of ideal biomarkers for liquid biopsies. They are extracellular vesicles containing DNA, RNA, lipids, and proteins, which they transfer between cells, serving multiple functions and being implicated in both the physiological processes and the pathogenesis of diseases. Of all the biomolecules contained in exosomes, microRNAs (miRNAs) seem to have the most clinical utility in the diagnosis and treatment of EC. Exosomal miRNAs mediate the communication between EC cells, cancer-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs) and have a pivotal role in the tumor cells' proliferation, epithelial to mesenchymal transition (EMT), and the formation of a tumor microenvironment. They participate in many processes that are tied to carcinogenesis and cancer progression, and they are therefore considered as attractive therapeutic targets. Here, we review the functions of exosomes in EC, focusing on potential biomarkers of diagnostic and prognostic significance or potential therapeutic use.

The Role of PROX1 in Neoplasia: A Key Player Often Overlooked.

The human PROX1 gene (Prospero homeobox gene 1) is a member of the homeobox transcription factor family. PROX1 plays a key role in the development of the lymphatic system and is primarily used as a lymphatic vessel marker. However, as the accumulating evidence indicates that PROX1 is also implicated in the tumorigenesis of various cancer types, the scientific community has attempted to elucidate its complicated function in neoplasia pathogenesis, as well as its utility in cancer diagnosis, prognosis, and therapy. PROX1 has been shown to participate in the complex molecular mechanisms affecting tumorigenesis and has been associated with a plethora of clinicopathological parameters, including tumor stage and patients' overall survival. Depending on the specific organ affected, PROX1 has exhibited both tumor-promoting and tumor-suppressing properties, with its inhibition and reactivation representing possible novel therapeutic interventions, respectively. Moreover, researchers have reported PROX1 as a useful tool in the fields of diagnosis and prognosis assessment. The current study aims to summarize and present the existing data that render PROX1 a novel and useful diagnostic and prognostic biomarker, as well as a possible therapeutic target.

Two Needle Passes Achieve Similar Diagnostic Yield Compared to Three Passes Regarding Diagnosis of Solid Pancreatic Lesions in Endoscopic Ultrasound-Guided Fine Needle Aspiration.

Current guidelines advocate 3-4 passes with a fine-needle aspiration (FNA) to achieve high rates of diagnostic samples for malignancy when performing endoscopic ultrasound (EUS)-guided sampling of solid pancreatic lesions, in the absence of on-site cytologic evaluation. The aim of this study is to compare 2 vs. 3 needle passes in EUS-FNA for solid pancreatic lesions in terms of incremental diagnostic yield and to identify factors associated with the procedure's outcome. In this retrospective study, 2 passes of EUS-FNA were found to have similar diagnostic yield compared to 3 passes for the diagnosis of solid pancreatic masses, suggesting that there might be no significant incremental tissue yield when 3 passes are performed.

Primary hepatic neuroendocrine tumor with exophytic growth: report of a case with diagnosis by fine needle aspiration biopsy.

BACKGROUND: Primary hepatic neuroendocrine tumor with exophytic growth is a unique entity. CASE: A 74-year-old man presented to our hospital with abdominal discomfort. Diagnostic imaging procedures revealed a 15 x 10-cm mass in the liver with exophytic growth. The tumor was adjacent to the stomach, and clinical suspicion of gastrointestinal stromal tumor of the stomach was very strong initially. The cytologic and immunocytochemical examination of aspirated material showed features similar to those of neuroendocrine tumor. Systemic staging procedures showed no evidence of metastasis or other primary site. The histopathologic results of the excised tumor confirmed the cytologic diagnosis. CONCLUSION: Primary neuroendocrine tumor with exophytic growth is a rare entity and can be diagnosed with cytology and immunocytochemistry.

Prevalence of different HPV types and estimation of prognostic risk factors based on the linear array HPV genotyping test.

The aim of the study was to evaluate the prevalence and risk factors of HPV in a gynecologic population attending outpatient clinics using two new molecular tests. The Amplicor HPV test and the Linear Array (LA) HPV Genotyping test were used for the detection of HPV DNA in 320 women. Multiple logistic regression was used to identify independent prognostic factors of HPV positivity. The agreement between the two methods in terms of their qualitative results was 89.3% (kappa: 0.63). Based on the LA results, the overall prevalence of HPV DNA was 49.1%, 95% confidence interval (95% CI: 43.5%, 54.7%). The prevalence of high-risk HPV types was 30.3%. The predominant types were HPV-6 (24.8%) and HPV-16 (20.4%). Among women with normal cytology, the prevalence of HPV was much higher in those presenting other findings, such as inflammation, than those without other abnormal findings (49.5% vs. 31.5%). On the basis of multivariate analysis, the risk of HPV infection was higher among women with multiple sexual partners [>3 vs. 1: OR = 3.1, 95% CI: (1.5, 7.2)], Pap smear findings [low/high-grade lesions vs. negative: OR = 2.8, 95% CI: (1.2, 6.5)], the presence of warts [yes vs. no: OR = 3.0, 95% CI: (1.5, 6.3)] and no history of child birth [no vs. yes: OR = 2.6, 95% CI: (1.0, 6.7)]. Younger age was an additional risk factor for HPV infection with carcinogenic genotypes [OR for 1 year increase = 0.93, 95% CI: (0.89, 0.98)].

Expression and clinical significance of focal adhesion kinase in the two distinct histological types, intestinal and diffuse, of human gastric adenocarcinoma.

Focal adhesion kinase (FAK), a non-receptor tyrosine kinase protein, acts as an early modulator of integrin signaling cascade, regulating basic cellular functions. In transformed cells, unopposed FAK signaling has been considered to promote tumor growth, progression and metastasis. The aim of this study was to assess the clinical significance of FAK expression in the two distinct histological types of human gastric neoplasia. FAK expression was assessed immunohistochemically in tumoral samples of 66 gastric adenocarcinoma cases, 30 intestinal and 36 diffuse type, and was statistically analyzed in relation to various clinicopathological characteristics, tumor proliferative capacity and patients' survival. In intestinal type carcinomas, enhanced FAK expression was significantly associated with increased tumor proliferative capacity (P = 0.012). In diffuse type carcinomas, FAK staining intensity was significantly correlated with tumor size (P = 0.026) and disease stage (P = 0.024), presenting also a borderline association with nodal status (P = 0.053). In diffuse type carcinomas, enhanced FAK expression was significantly associated with longer overall survival times (log-rank test, P = 0.014), being also identified as an independent prognostic factor in multivariate analysis (Cox regression, P = 0.016). In contrast, patients with intestinal type tumors and enhanced FAK expression were characterized by shorter overall survival times, without though reaching statistical significance (log-rank test, P = 0.092). The current data support evidence that FAK protein may be considered as a diagnostic and prognostic marker in gastric neoplasia. Further studies conducted on larger clinical samples and highlighting on the distinct impact of the two histological types are warranted to delineate the clinical significance of FAK protein in gastric neoplasia.

Study of T lymphocytes infiltrating peritoneal metastases in advanced ovarian cancer: associations with vascular endothelial growth factor levels and prognosis in patients receiving platinum-based chemotherapy.

INTRODUCTION: The presence of CD3(+) tumor-infiltrating lymphocytes (TILs) has been found to correlate with improved survival in epithelial ovarian cancer, but the association of TIL subpopulations with clinical outcome remains controversial. We performed a prospective analysis of TIL subpopulations from patients with epithelial ovarian cancer and their activation status and studied their association with prognosis. METHODS: Flow cytometric analysis was performed on TIL subpopulations isolated from 45 fresh ovarian tumor specimens, obtained during surgery, after mechanical dissociation and enzymatic degradation. Vascular endothelial growth factor and tumor necrosis factor alpha levels in ascites and serum were measured by enzyme-linked immunosorbent assay. RESULTS: Significantly increased numbers of CD56(+) cells (natural killer and natural killer-like T cells; P = 0.045), activated CD4(+)HLA-DR cells (P = 0.046), and activated CD8(+)CD25(+) cells (P = 0.028) were found in serous and endometrioid carcinomas compared with mucinous and clear cell carcinomas. A high percentage of CD4(+)CD25(hi) cells (regulatory T cells) and activated CD4(+)HLA-DR cells significantly associated with improved median overall survival (not reached vs 35 months [P = 0.0241] and not reached vs 35 months [P = 0.0144], respectively) and median progression-free survival (30 months vs 14 months [P = 0.0819] and 30 months vs 13 months [P = 0.0479], respectively). Vascular endothelial growth factor ascites levels were inversely correlated with CD14(+) (rho = -0.529, P = 0.001), whereas HLA-DR8(+)CD8 lymphocytes were inversely correlated with both ascites and serum vascular endothelial growth factor levels (rho = -0.494, P = 0.006, and rho = -0.586, P = 0.037, respectively). CONCLUSIONS: The presence of regulatory T cells and activated CD4(+) cells within the tumor microenvironment is associated with improved overall and progression-free survival in patients with ovarian cancer.

The Goodness-of-fit of the Fractal Dimension as a Diagnostic Factor in Breast Cancer.

A large number of studies have found that the fractal dimension increases with the progression towards pathological or more pathological states, but there are also studies that have demonstrated the opposite relationship. In this study, we calculate the nuclear box-counting fractal dimension of 109 malignant, 113 benign, and 80 normal isolated breast cells in order to investigate its possible diagnostic importance. We computed the fractal dimension and its goodness-of-fit (i.e., the r-squared value that describes how well the regression line fits the set of the measurements) for two different sets of box size lengths. The statistical analysis did not confirm an important diagnostic potential of the nuclear fractal dimension of isolated breast cells. However, the goodness-of-fit did display a diagnostic potential. The r-squared value may be able to serve as a complementary diagnostic parameter.

Elevated Hu-Antigen Receptor (HuR) Expression is Associated with Tumor Aggressiveness and Poor Prognosis but not with COX-2 Expression in Invasive Breast Carcinoma Patients.

Hu-antigen R (HuR), a RNA-binding protein, is considered to play a crucial role in tumor development and progression by stabilizing or regulating a group of cellular mRNAs of cancer-related genes, such as cyclooxygenase-2 (COX-2). The present study aimed to evaluate the clinical significance of HuR and COX-2 expression in invasive breast carcinoma. HuR and COX-2 protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissue sections obtained from 121 patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival. High HuR expression was positively associated with larger tumor size and advanced disease stage (p = 0.0234 and p = 0.0361, respectively), being more frequently observed in ER negative cases (p = 0.0208). High COX-2 expression was negatively associated with histological (p < 0.0001) and nuclear (p = 0.0033) grade and tumor cells' proliferative rate (p = 0.0015), being more frequently observed in luminal-A compared to other molecular subtypes (p = 0.0221). High HuR expression was associated with poor overall and disease-free patients' survival at both univariate (log-rank test, p = 0.0092 and p = 0.0004, respectively) and multivariate (Cox-regression analysis, p = 0.0223 and p = 0.0004, respectively) level. On the other hand, high COX-2 expression was associated with favorable overall and disease-free patients' survival merely at univariate level (log-rank test, p = 0.0389 and p = 0.0154, respectively). HuR expression was not associated with COX-2 expression (Spearman R = 0.1489, p = 0.1032). The present data support evidence that HuR is associated with tumor aggressiveness and poor prognosis in breast carcinoma, reinforcing its potential as promising therapeutic target in this type of neoplasia.

Imaging and Cytopathological Criteria Indicating Malignancy in Mucin-Producing Pancreatic Neoplasms: A Series of 68 Histopathologically Confirmed Cases.

OBJECTIVES: This study aims to evaluate the performance of clinical, imaging, and cytopathological criteria in the identification of high-grade dysplasia/carcinoma (HGD/Ca) in pancreatic mucin-producing cystic neoplasms. METHODS: Sixty-eight consecutive, histopathologically confirmed mucin-producing cystic neoplasms, evaluated by endoscopic ultrasound-guided fine-needle aspiration, were enrolled; specifically, 39 branch duct intraductal papillary mucinous neoplasms (BD-IPMNs), 21 main duct IPMNs, and 8 mucinous cystic neoplasms. The associations between HGD/Ca in histopathology and findings of endoscopic ultrasound and cytology, demographic, lifestyle, and clinical parameters were evaluated, separately in IPMNs and mucinous cystic neoplasms. RESULTS: Age 65 years or more was associated with HGD/Ca in IPMNs. In BD-IPMNs, cyst diameter 3 cm or greater (sensitivity, 68.8%; specificity, 65.2%), a mural nodule (sensitivity, 56.3%; specificity, 78.3%), main pancreatic duct diameter 5 to 9 mm (sensitivity, 50.0%; specificity, 87.0%), and suspicious cytology (sensitivity, 81.3%; specificity, 100%) signaled the presence of HGD/Ca. Similarly, in main duct IPMNs, suspicious cytology predicted HGD/Ca with high sensitivity (88.9%) and excellent specificity (100%). Regarding cytopathological criteria, in BD-IPMNs, HGD/Ca was associated with a high nuclear/cytoplasmic ratio, background necrosis, presence of papillary structures, hypochromatic nuclei, hyperchromatic nuclei, and major nuclear membrane irregularities (thickening and/or indentations). CONCLUSIONS: Clinical, imaging, and cytopathological criteria are useful in the identification of HGD/Ca in IPMNs.

Evaluation of ER, PR, MIB-1, pS2, and nuclear grade in FNA specimens of cT1 breast carcinomas: clinicopathological correlation.

Objectives were to determine oestrogen (ER), progesterone receptors (PR), and antigen related to ER (pS2) and to characterize their relationship with the cellular proliferation marker MIB-1 and the nuclear grade (NG) of the cancer cells, using fine-needle aspirates (FNA), as well as the evaluation of their clinical usefulness. The expression of ER, PR, pS2, and MIB-1 was preoperatively detected by immunocytochemistry in FNAs of 70 patients with breast adenocarcinoma and clinical tumor size up to 2 cm. The NG of the tumor cells was also assessed in these samples. We analyzed whether there was any correlation between these biocytologic markers and the invasion of ipsillateral axillary lymph nodes (LN), which were histologically identified after standard surgical treatment in each case. Of the 70 patients 50, 42.85, 50, and 41.42% were positive for ER, PR, pS2, and MIB-1, respectively. Only NG alone was strongly related to the invasion of the LN (P < 0.001). All the patients with NG1 (100%) tumors presented free LN, whereas the majority of those with NG3 (72.72%) had invaded LN (P < 0.001). Patients (14.28%) with NG1 expressed MIB-1, 85.71% ER or PR, and 71.42% pS2. Among the MIB-1-positive tumors a high proportion of NG3 (65.51%) was observed. This finding underlined a relationship between MIB-1 and NG (P < 0.05), identifying an aggressive cancer type. Remarkably 93.33% of the patients with positive MIB-1 and invaded axilla had NG3, whereas 66.66% of them expressed ER or PR and 40% pS2. The findings of the present prospective, multivariate study indicate that NG of the tumor cells, obtained from the preoperative FNAs of breast cancer patients, is a strong predictive marker for the axillary status and in parallel with MIB-1 expression can with sufficient accuracy be of clinical utility. ER, PR, or pS2 on the other hand did not show any relation to the LN status and were not dependent to NG or MIB-1.

Expression of DNA mismatch repair gene MSH2 in cytological material from lung cancer patients.

Mismatch repair genes encode for proteins responsible for the correction of bases incorrectly paired in the DNA. Loss of DNA mismatch repair activity has been associated with various cancers including tumors of the lung. In the present study, we have analyzed by immunocytochemistry the expression of MSH2 DNA repair gene in cytological material obtained by fine needle aspiration from a panel of 42 primary lung cancer patients. Specimens included 13 adenocarcinomas, 11 small cell carcinomas and 18 squamous cell carcinomas. Loss of expression or low expression was detected in 6 out of 13 (46%) adenocarcinomas and in 7 out of 18 (39%) of squamous cell carcinomas, although all 11 small cell carcinomas expressed MSH2. Our results suggest that loss of MSH2 expression is frequent in nonsmall cell carcinomas of the lung (P < 0.01, chi2 test). Evaluation of MSH2 expression can be applied for the screening of cytological material from fine needle aspirations from the lung.

Immunocytochemical panel for distinguishing between carcinoma and reactive mesothelial cells in body cavity fluids.

The morphological evaluation of cytological specimens from body cavity fluids presents difficulties in the differential diagnosis between benign reactive mesothelial (RM) cells and adenocarcinoma (AC) or malignant mesothelioma (MM). The aim of our study was to investigate whether a panel of five different antibodies can offer reliable markers in the differential diagnosis of RM, AC, and MM in serous effusions. A total of 134 cytological specimens of serous effusions from 80 ACs, 50 RMs, and 4 MMs, previously stained with Papanicolaou stain, were selected retrospectively from our files and stained with anti-human mesothelial cell (HBME-1), calretinin, epithelial specific antigen (MOC-31), Ber-EP4, and BG8. Statistical significance was found with HBME-1, calretinin, MOC-31, anti-human epithelial antigen (Ber-EP4), and blood group related antigen (BG8) when comparing AC vs. any type of mesothelial proliferation (MM or RM). The sensitivity of HBME-1 and calretinin for mesothelial cells was 98 and 100%, respectively, and the specificity was 71 and 80%, respectively. Both antibodies stained reactive mesothelial as well as MM cells, with calretinin showing a stronger intensity of immunostaining. The sensitivity of the stain for AC was 86.25% for MOC-31, 77.5% for Ber-EP4, and 67.5% for BG8, and, when combined, the sensitivity was 100%. Our data suggest that immunocytochemical studies performed on Papanicolaou-stained cytological smears with HBME-1, calretinin, MOC-31, Ber-EP4, and BG8 proved to be useful in the differentiation between metastatic AC and mesothelial proliferation. Probably, calretinin is a more preferred marker for mesothelial cells as evidenced by a more intense staining reaction.

Pregnancy associated breast cancer (PABC): aspects in diagnosis.

Diagnosis of a clinical entity like pregnancy associated breast cancer (PABC) is as demanding and challenging as its rarity. Increasing incidence and controversy that exists in the literature upon prognosis, tumor aggressiveness and underlying mechanisms, highlight the importance of optimizing the diagnostic strategy in women with PABC. Adjustment of standard approach for breast cancer by modifying management methods and options plays key role in decision making. Knowledge of diagnostic modalities and their limitations, in accordance with awareness of physiologic hormone-induced changes of pregnancy and lactation, is the fundamental method of diagnosis in PABC. Thorough triple assessment (history/clinical examination, imaging and cytology/histology) enforces healthcare providers with all essential tools to avoid detrimental delay in diagnosis and to confront with their own hesitation to take action due to limited experience of the disease.