The role of P53 and Bcl-2 proteins in 7, 12-dimethylbenz-(a)-anthracene-induced tumor growth.

7, 12- Dimethylbenz-(a)-anthracene (DMBA) has been used for a long time to induce rat mammary gland carcinogenesis. In a previous paper we described the effects of diet, of non-steroidal anti-inflammatory drugs and the combination of these two factors on breast cancer. We also pointed out that DMBA tumor generating process is still poorly understood. The present study attempts to explore whether P53 or the pro-apoptotic protein Bcl-2 are potential targets of DMBA in its induction of breast tumors in the Sprague-Dawley rat breast tumorigenesis model. Our results indicate that the DBMA-induced tumors are apparently the result of P53 inactivation. This inactivation results in tumorigenesis, probably aided by the absence of Bcl-2 in the tumor cells of the Sprague-Dawley rat animal model. We discuss the potential mechanisms by which P53 inactivation results in tumorigenesis.

Human pulmonary Dirofilariasis: one more case in Greece suggests that Dirofilaria is a rather common cause of coin lesions in the lungs in endemic areas of Europe.

Herein we describe a case of a 52 year-old male from Greece who presented with a coin lesion in the right lung, which proved to be an infection from Dirofilaria immitis. A careful review of the literature shows that, contrary to the common perception, humans may be frequently infected by Dirofilaria species. For this reason the authors suggest that in every case which presents with a coin lesion in the lung in endemic areas, dirofilariasis should always be considered, and excluded before any other intervention is decided.

Steroid receptor expression in human endometrium during the follicular phase of stimulated cycles.

BACKGROUND: No data are currently available regarding kinetics of human endometrial steroid receptors in stimulated cycles. METHODS: In 31 patients (age <39 years) stimulated with gonadotrophins and GnRH antagonists for intrauterine insemination (IUI) an endometrial biopsy was performed on the first day after the end of menstruation and a second biopsy was performed two (Group 0 + 2, n = 10) or four (Group 0 + 4, n = 11) days after the first biopsy, or on the day of hCG administration (Group 0 + hCG, n = 10). Expression of progesterone (PR) and estrogen (ER) receptor was investigated by immunohistochemistry using monoclonal antibodies. RESULTS: PR and ER levels were significantly increased in the second versus the first biopsy, in all groups analyzed (P = 0.01), in both stromal and glandular cells. Between the three groups compared, a significant increase in PR expression was observed for glandular cells (P = 0.03), with the highest value observed in Group 0 + 4. Moreover, the increase in PR expression in stromal cells differed between groups (P = 0.01), with the highest value observed in the Group 0 + hCG. CONCLUSIONS: In stimulated cycles for IUI, ER expression in both glandular and stromal endometrial cells, after an initial increase, does not appear to change significantly during the follicular phase. On the contrary, during the same period of time, following an initial rise, PR expression in glandular and stromal cells continues to increase.

Effects of rich-in-fat diets and highly selective COX-2 inhibitors on 7,12-dimethylbenz-(A)-anthracene-induced tumor growth.

The effects of diet, of non-steroidal anti-inflammatory drugs, or of their combination on carcinogenesis continue to be a case for controversy. Diets that are high in fat have been linked to increased risk of various tumors. At the same time there is substantial, but not conclusive, evidence that the risk of breast and colon cancer correlates with total fat intake rather than a specific type of fat. On the other hand, non-steroidal anti-inflammatory drugs (NSAIDs) have been studied extensively because they appear to delay or inhibit the development of malignant and pre-malignant lesions. 7,12-Dimethylbenz-(a)-anthracene (DMBA) has been used for a long time to induce carcinogenesis in a number of rat animal models. The present study attempts to identify the effects on DMBA-induced tumor growth (a) of diets rich in fat and (b) of the highly selective COX-2 inhibitor Celecoxib, which has been claimed to offer substantial protection against carcinogenesis.

Immunohistochemical investigation of metabolic markers fatty acid synthase (FASN) and glucose transporter 1 (GLUT1) in normal endometrium, endometrial hyperplasia, and endometrial malignancy.

BACKGROUND: Cancer cells present higher metabolic needs in comparison to their normal, non-neoplastic counterparts, consuming carbohydrates as a source of energy. Moreover, increased fatty acid biosynthesis is noted in many malignancies. In this regard, we investigated specific metabolic markers, the fatty acid synthase (FASN) which catalyzes fatty acid synthesis and the glucose transporter 1 (GLUT1) which promotes glucose transport through the cellular membrane, in normal endometrium, endometrial hyperplasia, and endometrial malignancy. METHODS: We examined the immunohistochemical expression of GLUT1 and FASN in 43 cases of endometrioid adenocarcinoma, 15 cases of serous endometrial carcinoma, eight cases of clear cell endometrial carcinoma, 11 cases of atypical hyperplasia / endometrial intraepithelial neoplasia, 17 cases of simple hyperplasia, and 20 cases of normal endometrium. RESULTS: We observed a gradual increase in the expression of both markers, progressing from benign clinical conditions to malignancy. The most notable finding concerned the difference of FASN immunoreactivity between atypical hyperplasia and grade 1 endometrioid adenocarcinoma (p =0.01). CONCLUSION: GLUT1 and FASN expression demonstrated a gradual increase when advancing from endometrial hyperplasia to carcinoma. These findings suggest that both GLUT1 and FASN immunohistochemistry might be used as an adjunct in the differentiation between atypical endometrial hyperplasia and endometrial carcinoma in complex cases. HIPPOKRATIA 2017, 21(4): 169-174.

Immunohistochemical expression pattern of metastasis suppressor KISS-1 protein in adenomyosis lesions and normal endometrium.

OBJECTIVE: Kisspeptins are multifunctional peptides; it has been shown that they act as inhibitors of tumor metastasis in a range of cancers and that they are also involved in cell invasion through regulation of matrix metalloproteinases (MMPs). The aim of this study was to investigate the expression of KISS-1 protein in adenomyosis lesions compared with matched eutopic endometrium, as well as with endometrium from patients without adenomyosis. STUDY DESIGN: In this comparative, non-interventional study, adenomyosis and corresponding eutopic endometrium samples from women with histologically proven adenomyosis after hysterectomy, and eutopic endometrium samples from women without adenomyosis were analysed. Expression of KISS-1 protein was analyzed immunohistochemically in formalin-fixed, paraffin-embedded adenomyotic tissue specimens (n=29), matched eutopic endometrium from the same patients (n=29) and normal endometrium from patients without adenomyosis (n=29). RESULTS: Using a semi-quantitative immunohistochemical score, we found that KISS-1 protein expression was higher in the adenomyotic as compared with matched eutopic glandular endometrium (p<0.05), in which in turn KISS-1 protein expression was higher than those from patients without adenomyosis (p<0.001). The inverse correlation was found in the stroma, between adenomyosis lesions and matched eutopic endometrium (p<0.01), while no statistically significant correlation was found in KISS-1 protein expression in the stroma between patients with and without adenomyosis. CONCLUSIONS: KISS-1 protein expression appears to be up-regulated in adenomyotic as compared with eutopic glandular endometrium of patients with, as well as women without adenomyosis. These findings are suggestive of the involvement of KISS-1 protein in the pathogenesis and maintenance of adenomyosis. Future studies should investigate whether KISS1 protein could be used as a marker for early and minimally invasive detection of adenomyosis, based on its differential protein expression pattern in the eutopic endometrium of patients with and without adenomyosis.

KIT expression in fetal, normal adult, and neoplastic renal tissues.

BACKGROUND: KIT is a transmembrane tyrosine kinase receptor, expressed in high amounts in various normal cells. In addition, c-kit mutation or activation is a major pathogenetic event in certain tumours (such as gastrointestinal stromal tumours). There are only limited data in the literature on the expression of KIT in normal and neoplastic renal tissues. AIMS: To investigate KIT expression in normal and neoplastic renal tissues. METHODS: KIT expression was evaluated by means of immunohistochemistry in paraffin wax embedded sections from 67 tissue samples. RESULTS: Eight of eight fetal kidneys, and 10 of 10 normal adult kidneys revealed cytoplasmic staining of renal tubules. The three cases of renal dysplasia studied expressed KIT in their normal and aberrant tubules. Two of 13 conventional renal cell carcinomas (RCCs), two of seven papillary type RCCs, four of seven chromophobe type RCCs, none of six nephroblastomas, seven of seven oncocytomas, two of two mesoblastic nephromas, and two of four angiomyolipomas were positive. CONCLUSION: KIT is expressed in normal fetal and adult renal tubules, and in a subset of renal tumours. The expression of KIT in these renal tumours may prove to have diagnostic relevance and/or therapeutic implications.

P53 codon 72 polymorphism and correlation with ovarian and endometrial cancer in Greek women.

The polymorphism of codon 72 in the p53 tumour suppressor gene has been associated in the last decade with the risk of developing various neoplasias. An influence of this polymorphism on ovarian and endometrial cancer has also been suggested. We examined the genotype frequency of this polymorphism in archival samples from 56 patients with endometrial neoplasias and 51 patients with ovarian neoplasias. Cervical smears from 30 healthy, human papillomavirus (HPV)-negative women with normal cytology and colposcopy, served as control sample. Women with ovarian neoplasias, especially adenocarcinomas, had Arg/Arg more often than healthy controls [odds ratio (OR) 4.16 at P = 0.0058]. No statistically significant difference was found between women with endometrial cancer and controls. Differentiation of ovarian tumours did not appear to be associated in a statistically significant manner with the genotype, whereas a positive linear trend of Arg/Arg towards poor differentiation was noted in endometrial malignancies (mainly endometrioid adenocarcinomas). Our results suggest that homozygous arginine at codon 72 of p53 may represent a risk factor for developing ovarian malignancies and may affect the differentiation of endometrial cancer. Further studies need to be carried out in order to establish the clinical use of this polymorphism for risk assessment and possibly outcome prediction of ovarian and endometrial neoplasias.

Breast-like cancer of the vulva: primary or metastatic? A case report and review of the literature.

A 45-year-old white female presented a polypoid nodule in the vulva, one year after she was operated on for breast cancer. Histologic examination showed a poorly differentiated carcinoma that closely resembled the primary breast tumor. Eight similar cases have been previously described in the literature. This very rare event should be differentiated from primary adenocarcinoma of the mammary-like glands of the vulva. The recognition of such a lesion as primary or metastatic is very important, since it greatly influences management and prognosis.

Ovarian capillary hemangioma and stromal luteinization: a case study with hormonal receptor evaluation.

BACKGROUND: Ovarian hemangiomas are rare tumors, most of them asymptomatic, and of the cavernous type. Six of the reported cases were accompanied by stromal luteinization. There is a debate whether these luteinized cells promote the growth of the vascular lesion or just represent a stromal reaction. CASE: A 71-year-old female was incidentally found to have a small capillary hemangioma in her left ovary, surrounded by a rim of luteinized stromal cells. Immunohistochemical investigation revealed the presence of estrogen and progesterone receptors in the endothelial cells of the lesion. CONCLUSION: Our histological and immunohistochemical findings, as well as data from the literature, support the view that at least some vascular lesions may result from hormonal stimulation.