Immunohistochemical assessment of p16, COX-2 and EGFR in HPV-positive cervical squamous intraepithelial lesions.

The protein capsid L1 of the human papilloma virus (HPV) - a key factor in the cervical carcinogenesis - is considered, together with p16, EGFR and COX-2, a characteristic marker for the evaluation of the malignancy progression and prognostic, in terms of tumoral aggressiveness. The purpose of the present study was to make a comparative assessment between the immunohistochemical pattern of p16, EGFR and COX-2 and immunochemical expression of L1 HPV capsid protein, in low grade and high-grade cervical squamous intraepithelial lesions, in order to determine the relationship of these tumoral markers with the infection status of HPV, and their practical applicability in patients diagnosis and follow-up. The study group included 50 women with cytological and histopathological confirmed LSIL (low grade SIL) and HSIL (high-grade SIL). The immunoexpression of L1 HPV protein was assessed on conventional cervico-vaginal smears and EGFR, COX-2 and p16 were immunohistochemically evaluated on the corresponding cervical biopsies. From all cervical smears, the HPV L1 capsid protein was expressed in 52% of LSIL and 23% of HSIL. From all cervical biopsies, p16 was positive in 64% of LSIL, 82% of CIN2 and 100% of CIN3, EGFR was overexpressed in 67% of HSIL (56% CIN2 and 43% CIN3) and 32% LSIL. For COX-2, the Allred score was higher in HSIL when compared to LSIL. Our data revealed 33 cases belonging to both LSIL and HSIL categories with the same Allred score. Immunochemical detection of L1 capsid protein, on cervico-vaginal smears, indicates an immune status induced by the HPV infection and may offer prognosis information, mainly in LSIL lesions. The assessment of p16, EGFR, and COX-2 allows to an integrative approach for the progression of squamous intraepithelial lesion, associated or not with the HPV infection.

Immunohistochemical evaluation of COX-2 expression in HPV-positive cervical squamous intraepithelial lesions.

Cyclooxygenase 2 (COX-2) regulates the prostaglandins production and it seems to have a role in the onset and progression of different malignant tumors, being overexpressed in numerous human malignancies and premalignant conditions. Some cellular elements from chronic inflammatory processes, together with stromal cells may be involved in neoplastic transformation of proliferative stem cells and in the process of tumor invasion. Cervical carcinoma, as a commonly pattern of different tumors, can express COX-2 in association with glutathione-S-transferase isoenzymes and can be considered as possible molecular targets in antitumoral therapy. The purpose of this study was to evaluate the expression of cyclooxygenase (COX)-2 in cervical squamous intraepithelial lesions of low-grade (LSIL) and high-grade (HSIL), with morphologic evidence of HPV infection. Immunostains with COX-2 antibodies were performed on formalin-fixed and paraffin-embedded tissue sections from 20 cervical biopsies: 10 with LSIL histopathologic diagnosis and 10 with HSIL histopathologic diagnosis. All LSIL biopsies and four HSIL cases (equivalent to CIN2) presented also intermediate squamous cells, with pathognomonic morphology of HPV infection (koilocytes). The Allred immunohistochemical score for the intensity of staining and the percent of cells stained was assigned. The slides were scored by three independent pathologists and compared across histological categories. Regarding the intensity of cytoplasmic COX-2 immunostaining, a weaker expression was observed in specimens with LSIL and a stronger one in those diagnosed with HSIL, the highest score being noted in HSIL corresponding to CIN3 lesions. The increase of COX-2 expression in cervical cancer precursors certifies that COX-2 may have a role in the development and progression of cervical squamous intraepithelial lesions.

Immunochemical assessment of p16 and HPV L1 capsid protein in cervical squamous intraepithelial lesions.

UNLABELLED: The behavior of the cervical squamous intraepithelial lesions cannot be predicted, many of them, particularly of the low grade type, may disappear without treatment. Invasive cervical carcinoma occurs in approximately 10% of the intraepithelial precursor lesions, being strongly associated with HPV infection. The aim of this study was to make a comparative assessment between immunohistochemical and immunocytochemical expression of p16 and L1 HPV capsid protein respectively, in low grade and high grade cervical squamous intraepithelial lesions. MATERIAL AND METHOD: The study involved 20 patients with cytological diagnosis of LSIL/CIN1 (low grade squamous intraepithelial lesion/cervical intraepithelial neoplasia) and HSIL (CIN2 and CIN3) (high grade squamous intraepithelial lesion), which underwent a subsequent cervical biopsy. The conventional smears were evaluated for the immunoexpression of L1HPV protein and the corresponding biopsies for the immunoexpression of p16. RESULTS: The HPV L1 capsid protein was expressed in 46% of LSIL and 24% of HSIL. P16 was positive in 68% of LSIL, 84% of CIN2 and 100% of CIN3. The correlative analysis of p16 status and protein L1HPV expression can be very useful in the assessment of progression risk of cervical squamous intraepithelial lesions.

[Diagnostic difficulties in mammary gland adenosis. Case report]. / Probleme de diagnostic in tumora adenozis a glandei mamare. Prezentare de caz.

Tumor adenosis represents a rare lesion, which most frequent appears as a palpable mass, with more than the usual dimensions. The paper presents a case of tumor adenosis of the mammary gland of a 16 years girl. Macroscopically, the tumor was well delimited, with gray-white surface and a nodular aspect on section. The tissue was processed by routine technique and stained with hematoxylin-eosine (H&E). There were also performed immunohistochemical (Actin SM, CK, S100) and special stainings (silver impregnation). Microscopically, there were observed several histologic types of adenosis, the most frequent being sclerosing adenosis. Through silver impregnation it was observed that the basement membrane, which surrounded the tubes, was intact. Immunohistochemically, there were evidentiated the epithelial and myoepithelial components of the tubes. The presence of these elements led through the diagnosis of tumor adenosis. The importance of recognition of the tumor adenosis is found in the possibility of wrong interpretation of this with tubular invasive carcinoma, these two entities being often mistaken, mainly at the frozen-section examination.

[Genital hematoma--local obstetrical trauma or pregnancy disorder?]. / Hematomul genital--traumatism obstetrical local sau disgravidie?

The general haematoma is a disease which appears during labour and affects the vulvar, vaginal or the parametrial tissues. The study of this affection implies the discussions of some special aspects, as the distinction between this disease and the traumatic complications of the labour; the observation that the genital haematoma is frequently associated with proteinuria and primiparity which leads to the possible inclusion of this disease among pregnancy toxaemias; the clinical importance of this affection, the severe forms prejudicing the mother's life. In the genital haematoma pathogenesis it is important to notice that this disease is the consequence of a vascular rupture, most frequently affecting the small vessels or the capillaries, and it is favoured by the increased vascular flow during gravidity and by the tissues' slip on the gravidic inhibition background. After mentioning the predisposing factors, details about the pathological anatomy are given and a new classification is proposed, mostly based on clinical and less on anatomical features. The clinical symptoms and the treatment are presented on a large scale, discussing the latest informations in the specialty literature.

[The role of lipid peroxidation and of the antioxidant systems in normal pregnancy and in pre-eclampsia]. / Rolul peroxidarii lipidice si al sistemelor antioxidante în sarcina normala si în preeclampsie.

Several recent studies have reported that there is an imbalance between increased oxidant status and decreased antioxidant system in women with preeclampsia; this factor may contribute to endothelial lesion, one of the characteristics of the disease. Our studies has examined serum levels of lipid peroxides and of some of the antioxidants (glutathione and glutathione-peroxidase) in women with preeclampsia compared with normal pregnant women. The study was realised on two groups: Group A consisting of 34 normal pregnant women and group B consisting in 20 women with PEC. Serum levels of lipid peroxides have been found markedly increased and of antioxidants markedly decreased in preeclamptic serum compared with normal gestational serum. Lipid peroxides are toxic compounds that damage endothelial cells, increase peripheral vasoconstriction and increase thromboxane synthesis. Our study has pointed out that in PEC there is a deficiency in the antioxidant system which allow, together with the ischemic placenta and activated neutrophils, the enhancement of lipid peroxides. This deficiency in AO system contribute to the development and aggravation of the clinical manifestation in PEC.

[THe role of biopsy in the early diagnosis of cancer of the cervix uteri]. / Rolul biopsiei în diagnosticul precoce al cancerului de col uterin.

Among the actions of early diagnosis of uterine cervix cancers, the sequence cytologic smear, colposcopy, cervix biopsy is well-known. The authors draw the attention that in some situations the cytologic smear and colposcopy are not sufficient and it is only biopsy that defines the nature of the lesion and may give therapeutic indications. Out of a series of 55 women to whom a cervix biopsy was performed, there were 27 cases in which biopsy was justified, showing either a severe lesion or the presence of koilocytes. The authors plead for a more frequent use of cervix biopsy as a means of early diagnosis of uterine cervix cancer or of its dysplasias.