The role of HSP90 molecular chaperones in hepatocellular carcinoma.

Misfolded proteins have enhanced formation of toxic oligomers and nonfunctional protein copies lead to recruiting wild-type protein types. Heat shock protein 90 (HSP90) is a molecular chaperone generated by cells that are involved in many cellular functions through regulation of folding and/or localization of large multi-protein complexes as well as client proteins. HSP90 can regulate a number of different cellular processes including cell proliferation, motility, angiogenesis, signal transduction, and adaptation to stress. HSP90 makes the mutated oncoproteins able to avoid misfolding and degradation and permits the malignant transformation. As a result, HSP90 is an important factor in several signaling pathways associated with tumorigenicity, therapy resistance, and inhibiting apoptosis. Clinically, the upregulation of HSP90 expression in hepatocellular carcinoma (HCC) is linked with advanced stages and inappropriate survival in cases suffering from this kind of cancer. The present review comprehensively assesses HSP90 functions and its possible usefulness as a potential diagnostic biomarker and therapeutic option for HCC.

Tailoring subtractive cell biopanning to identify diffuse gastric adenocarcinoma-associated antigens via human scFv antibodies.

Among various solid tumours, gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. Expansion into the peritoneal cavity, which results from dissemination of diffuse cancer cells, is the main cause of mortality in gastric adenocarcinoma patients. Therefore, investigation of putative biomarkers involved in metastasis is prerequisite for GC management. In an effort to discover potential tumour markers associated with peritoneal metastasis of GC, a semi-synthetic human scFv library (Tomlinson I) was used to isolate novel antibody fragments recognizing MKN-45, a poorly differentiated diffuse gastric adenocarcinoma cell line. Four rounds of subtractive selection each consisting of extensive pre-absorption of phage library with NIH-3T3 murine embryonic fibroblasts and AGS (a well-differentiated intestinal gastric adenocarcinoma) cell line were carried out prior to positive selection on MKN-45 target cells. ELISA-based screening of 192 phage-displayed scFv clones indicated 21 high-affinity binders with specific staining of MKN-45 compared with AGS cells. Diversity analysis of the selected phage-scFvs resulted in five distinct sequences with multiple frequency. Further analysis by ELISA and flow cytometry verified three clones that specifically recognized MKN-45 cells. Liquid chromatography-mass spectrometry analysis of the scFv-immunoprecipitated proteins has led to identification of c-Met, HSP90 α and HSP90 ß as candidate biomarkers associated with diffuse GC. Immunohistochemistry revealed the capability of purified scFvs to differentiate diffuse and intestinal gastric adenocarcinoma. Taken together, the isolated MKN-45-specific scFv fragments and their cognate antigens would be beneficial in screening and management as well as targeting and therapy of the diffuse gastric adenocarcinoma.

Clinical and histopathological outcome of cervical and chest MRI involving non-MRI-conditional cardiac pacemakers: a study using sheep models.

AIM: To examine the clinical and histopathological consequences of MRI in sheep implanted with non-MRI-conditional cardiac pacemakers. MATERIALS AND METHODS: Under general anesthesia, active fixation leads of two dual-chamber, non-MRI-conditional cardiac pacemakers (St. Jude Medical and Medtronic) were implanted either at the right ventricular apex or at the right atrium of two male sheep and connected to the V and A channels of the pacemakers, respectively. The generators were placed in cervical subcutaneous pockets. On day 5, both sheep underwent 1.5 T cervical and chest MRI with continuous electrocardiogram monitoring. Obtained sequences were T1-weighted (T1W), T2-weighted (T2W), T2-gradient echo and diffusion weighted (DW). The employed modes were OVO, VOO and VVI for one sheep and OAO, AOO and AAI for the other (unipolar and bipolar configuration of pacing and sensing for both). Battery impedance, pacing lead impedance, intrinsic amplitude and capture thresholds were checked at baseline and after each sequence, as well as 48 h after imaging. Histopathological examination of the cardiac tissue around the lead tip was performed 4 weeks post-imaging. RESULTS: No significant changes in device position or configuration were observed during or after MRI. Clinical outcome was uneventful in both sheep. Minor inflammatory and necrotic changes were reported after histopathological examination of the cardiac tissue around the lead tip. CONCLUSION: 1.5 T MRI of two implanted non-MRI-conditional pacemakers was found safe in terms of device configuration and stability, clinical outcome and cardiac tissue histopathological findings.

Moonlight human ribosomal protein L13a downregulation is associated with p53 and HER2/neu expression in breast cancer.

Breast cancer is the most common malignancy among females worldwide. Recent studies have shown extra-ribosomal roles of the moonlight ribosomal proteins in the development of human cancers. Accurate quantification of the gene expression level is based on the selection of the reference genes whose expression is independent of cancer properties and patient's characteristics. The aim of this study was the evaluation of the expression level of a previously proposed ribosomal protein as moonlight, L13a (RPL13A), in breast cancer samples and their adjacent tissues. Its association with genes of known roles in developing cancers was also investigated. Traditionally used housekeeping genes were selected and their expression was analyzed in 80 surgically excised breast tissue specimens (40 tumors and 40 tumor-adjacent tissues) by applying three software tools including GeNorm, NormFinder, and BestKeeper to select the most stable reference genes. Then, mRNA expression levels of RPL13A and p53 were evaluated. Additionally, protein expression levels of RPL13A were measured. It was demonstrated that PUM1 and ACTB are the most reliable reference genes and RPL13A is the least stable gene. There was a positive correlation between RPL13A and p53 mRNA expression levels in all the tumor samples. Moreover, significant downregulation of RPL13A expression levels was revealed in HER2+ tumor samples compared to HER2- ones. There was also a marked decrease in p53 mRNA expression levels in HER2+ tumor subtypes. Our results suggest that there is a probable relationship between RPL13A decreased expression with p53 and HER2/neu expression in the breast cancer.

RET Gene Analysis in Patients with Medullary Thyroid Carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor from the para follicular C cells of the thyroid gland. It occurs either sporadically or as part of an inherited syndrome. It is caused by an autosomal dominant mutation in the RET (Rearranged during Transfection) proto-oncogene. METHODS: The studied population consisted of 47 patients diagnosed with MTC in a specific population of northwest Iran along with their three children. Blood samples were collected from all subjects, genomic DNA was extracted and RET exons 10, 11, 13, 14, 15, and 16 were analyzed using PCR and direct sequencing. RESULTS: 32 missense mutations were identified in exons 10 (6.25%) and 11 (84.4%). Moreover, two novel mutations in codon 595 in exon 10 (E595D and E595A) and a new mutation in codon 689 exon 11 (S689T) were detected, and a new nucleotide change was found in exon 11 (T675T). Four different polymorphisms were also identified in exons 11, 13, 14, and 15. Based on our data, the frequency profile of RET mutations in the Azari population of Iran with MTC is 61.7%. The most frequent mutation in our population was C364G, whereas in most populations it is C634R. CONCLUSIONS: These results underline the importance of the genetic background of family members of any patient with MTC.

A positive correlation between immunohistochemical expression of CD31 and mast cell tryptase in odontogenic tumors.

In this study, we compared mast cell tryptase and CD31 expression between odontogenic tumors with the aim of predicting the clinical behavior of these lesions at the time of initial biopsy. We also evaluated the correlation between mast cell tryptase and CD31 expression to clarify the role of mast cells (MCs) in the growth of odontogenic tumors. Immunohistochemical staining with anti-MC tryptase and anti-CD31 antibodies was performed on 48 cases of odontogenic tumors including solid ameloblastoma (SAM), unicystic ameloblastoma (UAM), odontogenic myxoma (OM), cystic calcifying odontogenic tumor (CCOT) and adenomatoid odontogenic tumor (AOT). Ten high power fields were analyzed for each sample. Total MC count was significantly increased in SAM compared to other odontogenic tumors (p<0.05). Microvessel density was statistically higher in SAM and AOT compared to remaining odontogenic tumors (p<0.05). A significant correlation was observed between MCs and microvessels in odontogenic tumors (p=0.018, r=0.34). Our findings suggest a role for MCs in aggressive clinical behavior of odontogenic tumors. The significant correlation found between MC count and microvessel density in odontogenic tumors is in agreement with the theory of participation of MCs in tumor progression. Targeting MC activity may represent an important nonsurgical therapeutic approach, especially for aggressive odontogenic tumors.

A huge lymphangioma mimicking pleural effusion with extension to both chest cavities: a case report and review of literature.

Mediastinal lymphangioma is primarily a benign lesion and the majority of the cases are found incidentally. These lesions account for approximately 1% of all mediastinal tumors. Here we present a giant mediastinal cystic mass in a 35-year-old female who was presented with severe respiratory distress. On the plain chest radiography and CT scan, a massive left pleural effusion with large parasternal and mediastinal lymphadenopathy was seen. Thoracentesis was performed and 400 cm³ of clear fluid was drained from the left hemithorax. However, a subsequent CT scan with contrast and the same technique 40 days later showed a large cystic mass in the mediastinum protruding to the right and left hemi thoraces. The giant cystic mass was resected via right and left anterior thoracotomies. Histopathological examination revealed a diagnosis of lymphangioma. The patient has been alive and without tumor recurrence and has been followed for 2 years.

Median 10 years follow-up of patients with covert Cushing's syndrome: a case series.

BACKGROUND: Ectopic adrenocorticotropic hormone secretion syndrome occurs in 10% of all patients with adrenocorticotropic-hormone-dependent hypercortisolism. It is usually associated with overt malignancies or with occult and indolent tumors. This study aims to confirm the source of ectopic adrenocorticotropic hormone in four patients with ectopic Cushing's syndrome over time. CASE PRESENTATION: A 38-year-old Iranian man with Cushing's syndrome underwent bilateral adrenalectomy since the source of ectopic adrenocorticotropic hormone secretion was not localized and pituitary imaging was normal. A whole-body scan revealed a right-lung tumoral mass with mediastinal lymph node metastasis. The mass was assumed a lung carcinoid tumor with mediastinal adenopathy. Right-lung mid-zone lobectomy and mediastinal lymphadenectomy were done. In a 47-year-old Iranian man with Cushing's syndrome, whole-body computed tomography scan revealed a pulmonary nodule in the posterior segment of the left lower lobe of the lung. The third case was a 25-year-old Iranian man who presented with symptoms and signs of Cushing's syndrome. Pituitary magnetic resonance imaging revealed a microadenoma 5 × 9 mm. Whole-body scan showed abnormal focal somatostatin receptors analog avid lesion in the posterior aspect of inferior third of right lung, highly suggestive of ectopic adrenocorticotropic-hormone-producing tumor. The last case was a 43-year-old Iranian woman with Marfan syndrome with a history of mitral and aortic valve replacement and chronic dissection of the aorta, who presented with symptoms and signs of Cushing's syndrome. She underwent bilateral adrenalectomy 1 year later owing to failure to locate ectopic adrenocorticotropic hormone syndrome. Whole-body scan showed abnormally increased radiotracer uptake in the midline of the skull base and posterior aspect of the middle zone of left hemithorax and bed of left lobe of thyroid. CONCLUSION: The clinical spectrum of ectopic adrenocorticotropic hormone secretion syndrome is wide, and distinguishing Cushing's disease from ectopic adrenocorticotropic hormone secretion syndrome is difficult. Initial failure to identify a tumor is common. Pulmonary carcinoid or occult source of ectopic adrenocorticotropic hormone secretion syndrome is usually the cause. In occult cases of ectopic adrenocorticotropic hormone in which the tumor cannot be localized, serial follow-up with serial computed tomography, magnetic resonance imaging, or scintigraphy is recommended for several years until the tumor can be localized and treated.

Comparison of CD4+ and CD8+ T- lymphocyte in Helicobacter pylori-negative functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is the most common gastrointestinal disorder with several symptoms such as stomach pain and abdominal bloating. The aim of this study was to investigate and compare CD4+ and CD8+ in the Helicobacter pylori-negative functional dyspepsia and control groups. METHODS: Sixty one patients (35 patients with stomach pain and 26 with abdominal bloating), and 30 controls were reviewed based on the quantity of CD4+ and CD8+ T-cells isolated from gastric mucosa biopsy samples. The comparison between variables was analyzed with a chi-square or Fisher's exact test and logistic regression analyses. P<0.05 and odds ratio (OR) with a 95% confidence interval demonstrated statistical significance. RESULTS: A significant difference was observed between two-group patients and control group based on CD4+ and CD8+ presence, respectively (P=0.003, P=0.008). Furthermore, there was a significant difference between stomach pain-patients and control group with regard to CD4 count (P=0.01) and between abdominal bloating-patients and control group with regard to CD8 count (P=0.002). There was a decrease in both CD4+ and CD8+ T-cells in gastric mucosa in patients with FD with a significant reduction in the stomach pain-patients and abdominal bloating-patients in the number of CD4+ and CD8+ T-cells, respectively. CONCLUSION: These results indicated that the role of immunology in the absence of the CD4+ and CD8+ T-cells in the gastric mucosa may have a protective role against FD.

Diagnostic, prognostic, and therapeutic significance of miR-139-5p in cancers.

miRNAs are a group of non-coding RNAs that have regulatory functions in post-transcriptional gene expression. These molecules play a fundamental role in cellular processes, for instance cell proliferation, apoptosis, migration, and invasion. Scientific investigations have previously established that miRNAs can either promote or suppress tumor development by mediating different signaling pathways. miR-139-5p, located on chromosome 11q13.4, has been examined extensively in cancers. Studies have demonstrated that miR-139-5p might be an attractive cancer biomarker. Herein, we will review how miR-139-5p acts in cancer diagnosis, prognosis, and therapy, as well as elucidating its major target genes and associated signaling pathways.

Prognostic Impact of Monocyte to Lymphocyte Ratio in Clinical Outcome of Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: Lymphocyte to monocyte ratio (LMR) is a surrogate marker of systemic inflammation which is shown to be related to the patient's survival in multiple malignancies. An important implication of this marker potentially is neoplasms in which there is no correlation between prognosis and histopathological staging and also has no reliable chemical markers associated with prognosis. Herein, this meta-analysis aimed to investigate the prognostic role of LMR in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In the current systemic review and meta-analysis, we conducted a systemic search of databases and indexing sources, including PubMed, EMBASE, Cochrane, Scopus, and ProQuest up to May 2019 toinclude studies on the prognostic significance of LMR on patients with HCC. Overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) values were extracted from the studies and analyzed. The pooled hazard ratio with a 95% confidence interval was explored to identify the prognostic value of the LMR in the survival of the patients with HCC. RESULTS: A total of 12 studies with a total sample size of 3750 cases were included. There was significant heterogeneity among the studies; therefore, subgroup analysis was also performed. Overall analysis regarding OS showed an insignificant relationship between LMR and patient's prognosis, dividing to subgroups based on LMR cut-offs did not yield any significant result, subgroup analysis for RFS founded statistically significant results and LMR was significantly related to DFS. CONCLUSION: High LMR was associated with increased DFS and RFS, in return this association was not observed for OS.

The Role of Immunohistochemistry Studies in Distinguishing Malignant Mesothelioma from Metastatic Lung Carcinoma in Malignant Pleural Effusion.

BACKGROUND AND OBJECTIVE: Early diagnosis of malignant pleural mesothelioma (MPM) is the key point of its treatment. The main problem is the precise diagnosis of mesothelioma and its differentiation from metastatic lung adenocarcinoma. Mesothelioma exhibits complex immunohistochemical characteristics. The aim of this study was to study hybrid immunohistochemistry in the differential diagnosis of primary malignant pleural effusion from metastatic pulmonary cancers. MATERIAL AND METHODS: Twenty tissue samples in paraffin blocks from the pathology department of Imam Reza Hospital in Tabriz whose pathology reports cited mesothelioma or metastatic lung adenocarcinomas, were included in the studies. These tissues were deemed appropriate for IHC in terms of tissue quality and quantity. They were studied and evaluated for pathological markers. RESULTS: In patients with adenocarcinoma CK7 in 100% of patients (13 patients), TTF1 in 61.5% of patients (8 patients) and CEA in 53.8% of patients (7 patients) were positive, but HBME1 and Calretinin were negative for all patients. In patients with mesothelioma, HBME1 and Calretinin were positive in 100% of patients (7 patients) and TTF1, CEA and CK7 were negative. CONCLUSION: The results of this study showed that CEA, CK7, TTF1, Calretinin and HBME1 are suitable criteria for differentiating between metastatic lung adenocarcinoma and mesothelioma, and can differentiate the mesothelioma and adenocarcinoma with high accuracy.

Carunclar Mass as the Presenting Sign of Primary Orbital Liposarcoma.

This study aims to report a case of primary orbital liposarcoma which presented as caruncle mass. A 45-year-old woman presented to our hospital to evaluate the bumpiness of the caruncle in her left eye. A yellowish nodule , which was firmly attached to the sclera , was seen in the caruncle area and seemed to extend into the orbit. Incisional biopsy revealed myxoid liposarcoma She denied further evaluation and came back with enlarged mass after one year. She underwent lid-sparing exentration and was free of recurrence for 5 years.

Creutzfeldt-Jakob disease presenting with confusion and visual disturbance.

Creutzfeldt-Jakob disease is increasingly being reported in the last three decades as a result of increased awareness for the disease. Various studies have reported an annual incidence of 0.5-1.5 cases of Creutzfeldt-Jakob disease per million of general population. However, in our country, like other developing countries, the disease is still under-reported. Herewith, we described our clinical experience with an autopsy-proven case of Creutzfeldt-Jakob disease.

Immunohistochemical evaluation of myofibroblast density in odontogenic cysts and tumors.

Background. The aim of this study was to investigate myofibroblast (MF) density in a broad spectrum of odontogenic cysts and tumors and the relation between the density of MFs and the clinical behavior of these lesions. Methods. A total of 105 cases of odontogenic lesions, including unicystic ameloblastoma (UAM), solid ameloblastoma (SA), odontogenic keratocyst (OKC), dentigerous cyst (DC), radicular cyst (RC) (15 for each category), and odontogenic myxoma (OM), adenomatoid odontogenic tumor (AOT), calcifying odontogenic cyst (COC) (10 for each category), were immunohistochemically stained with anti-α-smooth muscle actin antibody. The mean percentage of positive cells in 10 high-power fields was considered as MF density for each case. Results. A statistically significant difference was observed in the mean scores between the study groups (P < 0.001). The intensity of MFs was significantly higher in odontogenic tumors compared to odontogenic cysts (P < 0.001). There was no statistically significant difference between odontogenic tumors, except between UAM and OM (P = 0.041). The difference between OKC and odontogenic tumors was not statistically significant (P > 0.05). The number of MFs was significantly higher in OKC and lower in COC compared to other odontogenic cysts (P = 0.007 and P = 0.045, respectively). Conclusion. The results of the present study suggest a role for MFs in the aggressive behavior of odontogenic lesions. MFs may represent an important target of therapy, especially for aggressive odontogenic lesions. Our findings support the classification of OKC in the category of odontogenic tumors.

Detection of survivin 2α gene expression in thyroid nodules.

CONTEXT: Functional studies of the survivin splice variants have been performed almost exclusively in various types of cancer and produced remarkable advances in our understanding of cancer biology and cancer genetics. AIM: To observation the expression of survivin 2α in thyroid nodules and estimate its potential as a new molecular marker in thyroid nodules screening and malignant thyroid, as well. SETTING AND DESIGN: We detected the expression of a splice variant of survivin, survivin 2α, in thyroid nodules. MATERIALS AND METHODS: Expression of survivin 2α mRNA was evaluated with specific primers by Hemi-Nested RT-PCR in 77 thyroid nodules including malignant and benign tumors, non-tumoral (goiter and thyroiditis) as well as surgical margin, non-neoplastic normal tissues adjacent to the malignant lesions. RESULT: Our data revealed for the first time the expression of survivin 2α in thyroid nodules. It was detected in 85.7% of non-neoplastic surgical margin tissues, 71.4% of non tumoral, 63.2% of tumoral samples. Also, the expression of survivin 2α in benign tumor samples (64.2%) is more than malignant groups (62.8%). CONCLUSION: Survivin 2α expression is the highest in non-neoplastic surgical margin rather than other samples and the lowest expression was that of malignancy. According to the results, it can be concluded that survivin 2α protein may be has a vital protective effect throw survivin quenching due to the high expression in normal tissue compared with lesions.

Transcriptional expression analysis of survivin splice variants reveals differential expression of survivin-3α in breast cancer.

Survivin, which is a novel member of the inhibitor of apoptosis family proteins, is known to play an important role in the regulation of cell cycle and apoptosis. Differential expression of survivin in tumor tissues introduces it as a new candidate molecular marker for cancer. Here we investigated the expression of survivin and its splice variants in breast tumors, as well as normal adjacent tissues obtained from the same patients. Thirty five tumors and 17 normal adjacent tissues from women diagnosed with breast cancer were explored in this study. Differential expression of different survivin splice variants was detected and semiquantitatively analyzed using reverse transcription-polymerase chain reaction. Results showed that survivin and its splice variants were differentially expressed in tumor specimens compared with normal adjacent tissues. The expression of survivin-3B and survivin-3α was specifically detected in tumor tissues compared with normal adjacent ones (53% in tumor tissues compared to 5% in normal adjacent for survivin-3B and 65% in tumor tissues and 0.0% in normal adjacent tissues for survivin-3α). Statistical analysis showed that survivin and survivin-ΔEx3 were upregulated in benign (90%, p<0.034) and malignant (76%, p<0.042) tumors, respectively. On the other hand, our results showed that survivin-2α (100% of the cases) was the dominant expressed variant of survivin in breast cancer. The data presented here showed that survivin splice variants were differentially expressed in benign and malignant breast cancer tissues, suggesting their potential role in breast cancer development. Differential expression of survivin-2α and survivin-3α splice variants highlights their usefulness as new candidate markers for breast cancer diagnosis and prognosis.

Immunohistochemical expression of Src protein in peripheral and central giant cell granulomas of the jaws.

AIM AND OBJECTIVE: The aim of this study was to investigate the expression of Src protein (an osteoclastic factor) in peripheral and central giant cell granulomas (PGCG and CGCGs) of the jaws and the relationship between the expression of this protein and the clinical behavior of these two lesions. MATERIALS AND METHODS: Thirty cases of PGCG and 30 cases of CGCG were immunohistochemically stained with Src. A staining-intensity-distribution (SID) score (proportion of stained cells × staining intensity) was used to evaluate immunoreactivity of the protein. Data were analyzed using statistical package for social sciences (SPSS) 17.0. RESULTS: There were no significant differences in the Src expression and the SID score between PGCG and CGCG. Furthermore, Spearman's rank correlation coefficient showed that there was a significant correlation between Src expression and SID score within both PGCG and CGCG (P < 0.001; r = 0.87 and 0.75, respectively). CONCLUSION: The findings of this study suggest that the multinucleated giant cells share some similarities with osteoclasts and Src protein can be used as a new therapeutic target to inhibit osteoclastic activity. In addition, differences in immunoreactivity of this osteoclastic protein do not reflect different clinical behaviors of PGCG and CGCG.

Immunohistochemical Analysis of p53, Ki-67, CD44, HER-2/neu Expression Patterns in Gastric Cancer, and Their Association with One Year Survival in North-West of Iran.

INTRODUCTION: Gastric cancer remains the second most common cause of cancer-related deaths worldwide. In many malignancies like, lung and breast, multiple prognostic factors are known, such as mutations in Ki-67, HER-2/neu, p53. In this study, we evaluated immunohistochemical protein expression patterns of cell-cycle-regulators p53, proliferation marker Ki-67, surface expression of CD44, HER-2/neu oncogene proposed as useful prognostic factors. METHODS: In this descriptive-analytic study, we evaluate 100 patients with gastric cancer who were referred to Shahid Ghazi Hospital or other oncology clinics of Tabriz University of Medical Sciences in 2005-2010. Patients with pathologic confirmation of gastric cancer were selected. Expression of p53, ki-67, CD-44, HER-2/neu were detected by immunohistochemical staining. RESULTS: In this study, 100 patients with gastric cancer participated. 76(76%) were men and 24(24%) were women with mean age of 64.02(8.05) years. Seventy two samples were intestinal type and 28 were diffuse type. CD44 was positive in 27(27%) patients. P53 was positive in 35(35%) patients. Ki-67 was positive in 53(53%) patients. HER-2/neu was positive in 51(51%) patients. CONCLUSION: The frequency of positive p53, Ki-67, CD44 and HER-2/neu varied in different studies. Positive Ki-67 and HER-2/neu were not associated with changes in survival but positive p53 and CD44 were significantly associated with improved survival.

Diagnostic value of protein Ki67 (MIB-1) in atypical pap smears of postmenopausal women.

BACKGROUND: Atrophic epithelium of cervix sampled from postmenopausal women may mimic high-grade cervical intraepithelial neoplasia in Papanicolaou-stained (Pap) smears. Ki-67 (MIB-1) protein presents on proliferating cells, and percentage of cells with positive nuclei provides a reliable tool for rapid evaluation of the growth fraction. The aim of this study was to determine the diagnostic value of protein Ki67 staining in atypical pap smears of postmenopausal women. METHODS: In a case-control setting, pap smears of 75 women with an atypical pap smear (case group) and 75 with normal pap smears (controls) were obtained before and after estrogen treatment. Afterward, samples were exposed to the monoclonal antibody Ki-67 (MIB-1) and the immunohistochemically demonstrated Ki-67+ cells were compared. RESULTS: Mean ages of cases and controls were 60.4±4.5 and 59.9±4.3 years respectively (P=0.50). There was one (2.7%) positive Ki-67 specimen in the case group, without any positive Ki-67 specimen in the control group (P=0.50). CONCLUSIONS: Measurement of proliferative activity index in Pap smears restrained with MIB1 is a simple, reliable, and cost-effective method for excluding negatives. This would imply that it might allow a substantial reduction of diagnostic estrogen courses and subsequent Pap smears in postmenopausal women with atypical findings.