Molecular and Immunohistochemical Characteristics of Complete Hydatidiform Moles.

Molar pregnancy is a gestational trophoblastic disease that belongs to the category of precancerous lesions. On the other end of the spectrum are gestational trophoblastic neoplasms such as invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor, which are considered malignant tumors. Based on defined histopathological criteria, molar pregnancy is divided into partial and complete hydatidiform mole. Especially in the case of early complete mole, the diagnosis can be quite challenging and often necessitates additional molecular or immunohistochemical methods. The aim of this study was to assess the importance of additional molecular and immunohistochemical methods to accurately diagnose complete hydatidiform mole and to stress the importance of correct diagnosis and close follow-up of these patients. A total of 367 consecutive cases of spontaneous abortion were analyzed in a 3-year period. Eight cases with histopathological diagnosis of complete molar pregnancy were selected for further analysis. Apart from standard microscopic analysis, additional molecular and immunohistochemical analyses were performed in all eight cases. Most of the histopathological characteristics of complete molar pregnancy were present in all cases, together with complete absence of positivity for the p57 immunohistochemical marker in the cytotrophoblasts and villous stromal cells. The molecular analysis revealed androgenetic diploidy in seven cases and biparental diploidy in one case with more than three consecutive complete molar pregnancies. Additional immunohistochemical and molecular methods can considerably aid in the correct diagnosis of molar pregnancy.

MicroRNA expression profiles in testicular biopsies of patients with impaired spermatogenesis.

Spermatogenesis is a complex process that involves thousands of genes whose expression during different stages is strictly regulated. Small non-coding microRNAs play an important role in the posttranscriptional regulation of mRNA processing during spermatogenesis. Using Agilent SurePrint v16 microRNA 8 × 60 K microarray kit, we investigated the microRNA expression profiles of 24 formalin-fixed paraffin-embedded testicular biopsies from patients with hypospermatogenesis (n = 10), hypospermatogenesis and azoospermia factor c region on the Y chromosome (AZFc) deletion (n = 3), Sertoli cell-only syndrome (n = 3) and maturation arrest (n = 2), in comparison with subjects with normal spermatogenesis (n = 6). After adjusting for multiple testing, six deregulated miRNAs were detected in the patients with AZFc deletion, 30 in maturation arrest group, 52 in Sertoli cell-only syndrome group of patients, and none in the group of patients with hypospermatogenesis. Some of the deregulated microRNAs were shared between groups, resulting in 58 unique differentially expressed microRNAs. The expression of five microRNAs (hsa-miR-34b, hsa-miR-449b, hsa-miR-517c, hsa-miR-181c, and hsa-miR-605) was validated by qRT-PCR in a total of 74 samples. Using mRNA expression profiles of subjects with matching histopathological patterns of impaired spermatogenesis from publically available Gene Expression Omnibus data sets, we have performed integrated mRNA-microRNA regulatory network analysis. Pathway analysis revealed significantly enriched set of genes for tumor necrosis factor-related apoptosis-inducing ligand signaling pathway, previously shown to be involved in regulation of apoptosis in normal functioning testis. Our results should be considered as preliminary as we have analyzed only a small number of patients in each studied group. Further studies with larger number of patients with impaired spermatogenesis as well as more targeted approaches with parallel microRNA and mRNA expression profiling in isolated subpopulations of somatic or germ cells from different stages of spermatogenesis are needed to clarify the role of the microRNAs in the process of spermatogenesis.

Expression of p53 protein product in triple negative breast cancers and relation with clinical and histopathological parameters.

INTRODUCTION: "Triple" negative breast cancer is a subgroup of so-called basal-like breast cancer. They are represented with 15% of all breast cancers, characterized with lack of hormone receptor as well as with negative expression of HER2 test. These tumors are more frequent in Afro-Americans and Latin-Americans, in patients with BRCA1 mutations and in patients with recent delivery. The aim of this study is to present the immunohistochemical and clinico-pathological characteristics of the triple negative breast cancer and their correlation with expression of the protein product of the tumor suppressor gene p53. METHODS: A retrospective analyses of 24 patients with triple negative breast cancer was performed. All of the patients were evaluated in the Histopathological Laboratory of the Clinical Hospital Sistina, during the period from June 2009, until June 2011. The standard immunohistochemical procedures, including the hormone receptor status, HER2 status, proliferative index - Ki67 and p53 gene protein product were performed, as well as additional immunohistochemical staining for so-called basal keratins (Cytokeratin 5/6 and high molecular weight cytokeratin 34BE12). RESULTS: The age of the patients ranged from 29-77 years. Positive lymph nodes were found in 14 (59%) patients. The tumor was poorly differentiated in 19 patients (79%). Overexpression of the p53 protein product was evaluated in 19 (79%) of the cases. All p53 negative patients (5/5) had poorly differentiated tumors (G3), associated with positive regional lymph nodes. The p53 positive group expressed quite opposite correlation, only 9/19 (47%) were with positive lymph nodes (p = 0.03). The expression of p53 protein product was also associated with the nuclear grade (p = 0.005), the mitotic index (p = 0.001), lymph-vascular invasion (p = 0.005) and with the proliferation index Ki67 (p = 0.003). There was a trend for association with the tumor size - pT (p = 0.05). CONCLUSION: According to the results, the triple negative breast cancers are subgroup of the poorly differentiated neoplasms frequently associated in the younger age groups. The majority of these have overexpression of the p53 protein product, which in other hand, are inversely correlated with lymph nodes metastases. Hence, the necessity of enriching the immunohistochemical protocol of these patients with new antibodies, in order to evaluate their expression, which would be helpful for prediction the outcome of different therapeutical modalities.

Isolated malignant peripheral nerve sheath tumor of kidney capsule.

The occurrence of an isolated malignant peripheral nerve sheath tumor (MPNST) of the kidney capsule is extremely rare and its presence may only be expressed by an insidious onset of non-specific and misleading symptoms with a predominance of lower back pain. A computer tomography (CT) scan (as the imaging procedure of choice) will demonstrate the tumor location and its relation to the surrounding structures. Tumor excision in toto is considered the treatment of choice, but it can be hazardous, especially if the tumor is adhering to the surrounding structures. Severe bleeding complications due to the damage of venous structures have to be considered, and establishing hemostasis may pose considerable difficulties. Therefore surgery should be attempted with full precautions and the patient must receive preoperative counseling. If malignancy can safely be excluded, a laparoscopic excision should be considered as an alternative treatment as recurrence is unlikely. Definition of the originating nerve might not always be possible, and a minor degree of neurological impairment has therefore to be anticipated. A case of an isolated MPNST of the kidney capsule without neurofibromatosis is presented. The tumor was located in the fatty and fibrous capsule. It was surgically removed. The patient was further managed with radiotherapy and chemotherapy. An MPNST in such a location is very unusual.