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Biomedical subjects

I Fayt

Publications and source records attributed to I Fayt.

At least 19 recordsLinked to original sources
PubMed2003

Cervical response to vaccination against HPV16 E7 in case of severe dysplasia.

OBJECTIVE: To evaluate the tolerance to vaccination against human papillomavirus (HPV)16 E7 (in SB adjuvant ASO2B) and its histological and immunohistological effects on HPV16 associated high-grade cervical dysplasias associated with HPV16. STUDY DESIGN: Five patients with histologically demonstrated severe cervical dysplasia (CIN3) HPV16 positive were injected three times before conization was performed 2 months after the first injection. We studied cytological, histological, proliferative pattern and immune profile before and after vaccination. The slides were compared with those obtained from non-injected patients. RESULTS: The injections were well tolerated and the specimens displayed a limited regression of the lesions. Nevertheless, massive CD4 and CD8 T cell lymphocytic infiltration was noticed after vaccination. DISCUSSION: We conclude that the vaccination we used provides an obvious immune histological reaction in the HPV infected cervix and that the 2 months delay before the final step (conization) is done is probably too short.

Adolescent↗
PubMed2002

Ki-67 immunostaining activity is higher in positive axillary lymph nodes than in the primary breast tumor.

BACKGROUND: The monoclonal antibody Ki-67 allows to investigate the proliferative activity of tumor and is a clinically useful marker to characterize breast cancer. In this study, we have compared Ki-67 activity in 38 primary breast tumors and in their respective positive axillary lymph nodes (ALNs). METHODS: Immunohistochemistry with the monoclonal antibody against Ki-67 was performed in 38 nodes positive breast carcinomas and in their respective positive ALNs. Statistical analysis was performed with the Student's t-test (2-tailed) for equality of means. RESULTS: The proliferation index measured by Ki-67 expression was significatively higher (p < 0.02) in ALN than in the primary tumor (29.8% v.s. 21.8%). CONCLUSION: These results strongly suggest a higher proliferation and perhaps aggressivity of metastatic neoplastic cells when compared with their respective primary tumor. Perhaps, in the future, these differences in proliferation behavior might be taken into account when considering the choice of the adjuvant therapy.

Adult↗
PubMed2002

An immunohistochemical study of abnormal keratinocyte proliferation in molluscum contagiosum.

BACKGROUND: Molluscum contagiosum is a common cutaneous tumour that is characterized by usually spontaneous involution and self-limited spreading in immunocompetent individuals. OBJECTIVE: We aimed to investigate the apoptosis and the expression of cell-cycle proteins in molluscum contagiosum lesions. METHODS: The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL)-based apoptotic index and the expression of the cell-cycle proteins Ki-67, p53, p21WAF and Bcl-2 were investigated in molluscum contagiosum lesions obtained from the trunk of 20 immunocompetent patients and in normal skin samples from the trunk of six healthy volunteers. RESULTS: Whereas molluscum contagiosum lesions displayed a TUNEL-based apoptotic index similar to that of normal skin, they exhibited an increased Ki-67 index, which was confined to the basal and first suprabasal layers (P < 0.001). Compared with normal non-sun-exposed skin, molluscum contagiosum lesions also exhibited increased p53 staining in basal cells (P < 0.01), increased p21WAF in suprabasal cells (P < 0.001) and loss of Bcl-2 expression. CONCLUSIONS: These results indicate that molluscum contagiosum lesions exhibit an increased proliferation rate of keratinocytes, which is likely to be partially counteracted by accumulation of p53.

Apoptosis↗
PubMed2002

Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis.

BACKGROUND: The aim of this study was to investigate a possible role for nerve growth factor (NGF) in the mechanism of pain and hyperalgesia induced by deep adenomyotic nodules and other forms of endometriosis and to clarify the relationship between endometriotic lesions and the surrounding nerves. METHODS: Endometriotic lesions (deep adenomyotic nodules, peritoneal endometriosis, ovarian endometriosis) and eutopic endometrium were obtained from 51 patients presenting with pain. Patients were allocated to two groups (group 1: patients with a deep adenomyotic nodule (n = 23); group 2: patients with peritoneal and/or ovarian endometriosis but without deep adenomyotic nodule (n = 28). Immunohistochemistry with antibodies against NGF, NGF specific tyrosine-kinase receptor (Trk-A) and S-100 protein was performed. Results were expressed as mean H-scores +/- SD, and correlated with the presence of hyperalgesia. RESULTS: The percentage of patients presenting hyperalgesia at physical examination was significantly higher in group 1 (96%) than in group 2 (11%) (P < 0.001). NGF expression was significantly stronger in deep adenomyotic nodules (DAN) than in ovarian (OE) and peritoneal endometriosis (PE), both in the proliferative phase in the glands [DAN: 226 +/- 18; OE: 140 +/- 9 (P < 0.001); PE: 110 +/- 7 (P < 0.001)] and in the stroma [(DAN: 204 +/- 21; OE: 125 +/- 15 (P < 0.001); PE: 100 +/- 9 (P < 0.01)]. NGF expression in DAN is also significantly stronger than in OE and PE in the secretory phase in the glands [DAN:181 +/- 32; OE: 85 +/- 3.3 (P < 0.001); PE: 65 +/- 9 (P < 0.001)] and in the stroma [DAN: 173 +/- 28; OE: 85 +/- 3.7 (P < 0.001); PE: 35 +/- 13 (P < 0.001)]. Perineurial and intraneurial invasion by endometriotic lesions were found only in deep adenomyotic nodules and not in the other forms of endometriosis. The specific receptor for NGF (Trk-A) is expressed in all the nerves that were included in the biopsies. CONCLUSIONS: These results suggest a role of NGF in endometriotic pain and hyperalgesia in deep adenomyotic nodules. The strong expression of the NGF-TrkA pathway in deep adenomyotic nodules could explain why this type of lesion infiltrates in richly innervated anatomical sites.

Adult↗
PubMed2001

Persisting active and proliferative intrinsic ureteral endometriosis under GNRH agonists therapy: a case with immunohistological study.

We report the case of a 30-year-old patient who underwent a segmental ureteral resection with ureteroureterostomy because of the presence of a left ureterohydronephrosis caused by an intrinsic ureteral endometriotic lesion. Preoperatively, the patient received a 3 months course of GNRH agonists. The serum estradiol level was at 12 pg/ml at the moment of surgery. Histology and immunohistochemistry performed on the resected specimen showed the presence of numerous large haemorrhagic endometriotic foci containing very high levels of alpha-estrogen and progesterone nuclear receptors, a high Ki-67 labeling index and a strong positivity for EGF-receptor. This is the first report of immunohistochemical study performed on ureteral endometriosis preoperatively treated with GNRH agonists. Because hormonal treatments are often prescribed in the treatment of ureteral endometriosis, clinicians should be aware of the possibility of persisting very active and proliferative ureteral endometriotic lesions even under treatment with GNRH agonists and very low levels of circulating estradiol.

Adult↗
PubMed2001

Evidence of human papilloma virus infection but lack of Epstein-Barr virus in lymphoepithelioma-like carcinoma of uterine cervix: report of two cases and review of the literature.

Lymphoepithelioma-like carcinoma (LELC) of uterine cervix is an uncommon variant of squamous cell carcinoma (SCC). We report here 2 new cases in which DNA sequences from human papilloma virus (HPV) types 16 and 18 were detected by polymerase chain reaction (PCR). To the best of our knowledge, HPV infection has not been previously described in similar cases occuring in European women. Moreover, Epstein-Barr virus (EBV), which is frequently associated with cervical LELC in Asian women, was absent in our 2 cases. These results suggest that HPVs but not EBV can play a role in the pathogenesis of LELC occuring in women originating from Western countries.

Carcinoma, Squamous Cell↗
PubMed2001

Warty carcinoma of the anus: a variant of squamous cell carcinoma associated with anal intraepithelial neoplasia and human papillomavirus infection.

Warty carcinoma (WC) is a rare variant of squamous cell carcinoma primarily described in the vulva in younger women and classically associated with human papillomavirus (HPV) infection. The gross findings are similar to those of verrucous carcinoma with large, exophytic tumors with a papillomatous surface. Microscopically, the tumor is papillated and contains fibrovascular cores covered by hyperkeratotic epithelium showing presence of koilocytes. We report a case of anal squamous cell carcinoma showing similar features, occurring in a young immunosuppressed male patient with a history of multifocal anal intraepithelial neoplasia (AIN). HPV-16 has been demonstrated both in the WC and in adjacent AIN, but the HPV status appears different in the two lesions: integrated in WC and episomal in AIN lesions. We also have demonstrated by immunohistochemistry that both WC and AIN are highly proliferative entities sharing the same MIB-1 pattern, and that WAF1/CIP1 protein expression is common in the two lesions irrespective of p53 protein expression.

Adult↗
PubMed2000

Overexpression of 27-kDa heat shock protein relates to poor histological differentiation in human oesophageal squamous cell carcinoma.

AIMS: Various stress conditions such as heat, chemical and mechanical stresses are known to play a major role in oesophageal squamous cell carcinoma development. Our goal was to evaluate whether changes in stress-induced 27-kDa heat shock protein (HSP27) expression could be demonstrated during oesophageal carcinogenesis. METHODS AND RESULTS: HSP27 expression was studied using immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections from 21 oesophageal squamous cell carcinomas occurring in smokers and/or alcohol abusers. Oesophagus from healthy patients (controls) (five), chemical (eight) and infectious oesophagitis (six) were also included in the study. In normal oesophagus, the protein is present only in the upper epithelial layers. In contrast, in chemical or infectious oesophagitis its expression is strong and occurs in all the epithelial layers including the basal layer. In non-tumoral oesophageal mucosa from smoking and/or drinking patients adjacent to invasive carcinoma, the distribution of the protein is patchy and irregular. In malignant areas, HSP27 protein expression increases drastically from dysplastic lesions to invasive carcinoma, being highest in the less differentiated areas. CONCLUSIONS: In human oesophagus, HSP27 expression is induced by various stresses but alcohol and tobacco generate focal perturbations in the stress response. Tumour immunoreactivity for this protein increases with the anaplasia of the tumour, as in some other tumours in which it is considered to play a role in drug resistance. To our knowledge, these data have not been previously described for oesophageal squamous cell carcinoma.

Carcinoma, Squamous Cell↗
PubMed2000

Smooth muscles are frequent components of endometriotic lesions.

Deep infiltrating endometriosis (deeper than 5 mm under the peritoneum) often takes the form of a nodular lesion (or 'adenomyotic nodule') consisting of smooth muscles and fibrosis with active glands and scanty stroma. Thus, among endometriotic lesions, a certain distinction is drawn between musculo-glandular lesions and glandular lesions composed of endometrial-like epithelium surrounded by a cell-producing (cytogenous) stroma. The aim of this study was to detect by immunohistochemistry, with a monoclonal antibody against muscle-specific actin, the presence of smooth muscles in 54 endometriotic lesions originating from four different pelvic locations (peritoneum, ovary, rectovaginal septum and uterosacral ligaments) and to quantify the smooth muscle content. Smooth muscles were frequent components of endometriotic lesions in pelvic locations. In addition, smooth muscles were significantly (P < 0. 001) more abundant in endometriotic lesions than in their respective unaffected sites. This finding supports, at least partially, the occurrence of a metaplastic phenomenon in the pathogenesis of endometriotic lesions. The definition of distinct endometriotic entities based on the difference in the tissue composition of the lesions (endometriotic nodules versus adenomyotic nodules) is inconsistent with the very frequent presence of smooth muscle cells in endometriosis irrespective of its localization.

Actins↗
PubMed2000

Sigmoid endometriosis and ovarian stimulation.

In-vitro fertilization (IVF) and ovarian stimulation are frequently performed in patients with endometriosis. Although endometriosis is a hormone-dependent disease, the rate of IVF complications related to endometriosis is low. We report four cases of severe digestive complications due to the rapid growth of sigmoid endometriosis under ovarian stimulation. In three patients, sigmoid endometriosis was diagnosed at laparoscopy for sterility. Because of the absence of digestive symptoms or repercussion on the bowel, no bowel resection was performed before ovarian stimulation. All patients experienced severe digestive symptoms during ovarian stimulation, and a segmental sigmoid resection had to be performed. Analysis of endoscopic and radiological data demonstrated that bowel lesions of small size may rapidly enlarge and become highly symptomatic under ovarian stimulation. At immunohistochemistry, these infiltrating lesions displayed high populations of steroid receptors and a high proliferative index (Ki-67 activity), suggesting a strong dependence on circulating ovarian hormones and a potential for rapid growth under supraphysiological oestrogen concentrations. Clinicians should be aware of this rare but severe digestive complication of ovarian stimulation. The early diagnosis of such lesions may help the patients to avoid months of morbidity falsely attributed to ovarian stimulation side effects. Further experience is necessary to determine the optimal attitude when diagnosing a small and asymptomatic endometriotic bowel lesion before ovarian stimulation.

Adult↗
PubMed2000

Relationship between endometriotic foci and nerves in rectovaginal endometriotic nodules.

The histological relationships between fibrotic tissue, endometriotic foci and nerves in the rectovaginal septum endometriotic or adenomyotic nodule were studied. This is considered to be one of the most severe forms of deep endometriosis. Masson's trichrome staining for fibrosis detection and immunohistochemistry with the S100 monoclonal antibody for nerve detection were performed in 28 rectovaginal endometriotic nodules from patients presenting with severe dysmenorrhoea and deep dyspareunia (23 patients with no other endometriotic location or potential cause of pain at laparoscopy and ultrasonography; five patients with multiple pelvic endometriotic localizations and other potential causes of pain at laparoscopy). Patients were allocated to two groups on the basis of their preoperative pain scores for pelvic pain, dysmenorrhoea and deep dyspareunia (group 1, score >7; group 2, score < or =7). For each symptom, the mean number of nerves and endometriotic lesions per high-power field and the mean largest diameter of the lesions were not statistically different in groups 1 and 2. The mean percentages of nerves located within the fibrosis of the nodule and within endometriotic lesions were significantly higher in group 1 than in group 2. Among nerves located within endometriotic lesions, there was a significantly higher proportion showing intraneurial and perineurial invasion by endometriosis in group 1 than in group 2. In rectovaginal endometriotic nodules, there was a close histological relationship between nerves and endometriotic foci, and between nerves and the fibrotic component of the nodule. We postulate that such topographical relationships could at least partially explain the strong association between this lesion and pain.

Adult↗
PubMed1999

Penile intraepithelial neoplasia overlying Kaposi's sarcoma lesions: role of viral synergy?

Several viral agents have been detected in the lesional tissue of Kaposi's sarcoma (KS). Their precise oncogenic role remains to be determined. A 32-year-old heterosexual man with acquired immunodeficiency syndrome (AIDS) who had penile lesions of KS with overlying epithelial changes characteristic of intraepithelial neoplasia associated with concurrent infection by human papillomavirus (HPV) and human herpesvirus 8 (HHV-8) is reported. The absence of viral DNA from uninvolved skin suggests that this coinfection is more than coincidental and may involve synergy between these viruses, as has already been suggested for HPV and herpes simplex 2 virus.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Correlation and prognostic significance of p53, p21WAF1/CIP1 and Ki-67 expression in patients with superficial bladder tumors treated with bacillus Calmette-Guerin intravesical therapy.

PURPOSE: We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21WAF-1-CIP1 (a critical downstream effector of p53 pathway of cell growth control, inhibiting cyclin dependent kinases) and the cell proliferation marker Ki-67 (MIB-1) could be used as prognostic markers of response to BCG in patients with superficial bladder tumors. MATERIALS AND METHODS: The study included 47 patients with superficial bladder tumors at high risk for recurrence or progression treated with 6 weekly intravesical BCG instillations. We analyzed p53, p21 and Ki-67 on paraffin embedded samples by immunohistochemistry and the percentage of positive cells was determined in a blinded fashion. Quantitative immunostaining was analyzed in relation to time to recurrence and progression using univariate or multivariate analysis and the Kaplan-Meier method. RESULTS: During a mean followup of 24.6 months 23 of the 47 patients (48.9%) presented with tumor recurrence and 10 (21.2%) had later progression to invasive disease. A p21 over expression (greater than 10%) was observed in 23 tumors (48.9%) and positively correlated with p53 (p = 0.0097) but not with Ki-67 (p = 0.327). Of the tumors 18 (38.2%) were p53 and p21 negative. Among p21 positive tumors 15 (65.2%) were p53 and p21 positive, suggesting that p21 may also be regulated by p53 independent pathways. However, p53 did not act as a predictor of recurrence or progression. In contrast, using Kaplan-Meier curves p21 over expression (greater than 10%) and Ki-67 at a 25% cutoff were associated with shorter recurrence-free survival (both p = 0.02 log rank test) but they did not predict additional information about risk of progression. However, multivariate analysis failed to demonstrate any independent prognostic value for p21 or Ki-67 in contrast to tumor stage. CONCLUSIONS: Our results indicate that p21WAF-1-CIP1 seems to be regulated by p53 independent pathways in superficial bladder cancer. The present study did not indicate an independent prognostic significance in patients treated with BCG for p53, p21WAF-1-CIP1 or Ki-67 markers. Larger prospective studies are needed to evaluate further the independent value of these biological markers in superficial bladder cancer management.

Adjuvants, Immunologic↗
PubMed1999

Pre-Kaposi's sarcoma: an expansion of the spectrum of Kaposi's sarcoma lesions.

We report on a lymphoedematous form of classic Kaposi's sarcoma (KS) in which characteristic purplish lesions were surrounded by atypical oedematous, flesh-coloured papules. Histological examination of these papular lesions revealed a proliferation of grouped, rather thick-walled capillaries with inflammatory infiltrates. Hot-start PCR amplification with KS 330-233 primer sequences demonstrated the presence of human herpesvirus 8 (HHV-8) sequences. In addition, cells isolated from these oedematous papules showed morphological and immunohistochemical features similar to those reported for KS-derived spindle cells. As a whole, these results suggest that these oedematous papular lesions represent pre-KS lesions and may expand the clinico-pathological spectrum of KS. The role of oedema in their induction is discussed.

Aged↗
PubMed1998

Chronic rejection of major histocompatibility complex class II-disparate skin grafts after anti-CD3 therapy: a model of antibody-independent transplant vasculopathy.

BACKGROUND: Chronic rejection remains a leading cause of allograft loss. Histologically, it is characterized by arterial intimal thickening and parenchymal fibrosis. The immune mechanisms triggering chronic rejection are still uncompletely understood. METHODS: We performed major histocompatibility complex (MHC) class H-incompatible skin grafts from C-H2bm12 (bm12, H2bm12) into C57BL/6 (C57BL/6, H2b) recipients immunosuppressed with a short course of anti-CD3 monoclonal antibodies to prevent acute rejection. RESULTS: More than 80% of grafts survived for prolonged periods, but eventually all displayed macroscopic and microscopic evidence of chronic rejection. At histology, there was a progressive arterial intimal thickening as well as intense dermal fibrosis. This was accompanied by an inflammatory infiltrate consisting of lymphocytes and macrophages, but also of a considerable number of eosinophils. Mice with chronic rejection were unable to generate anti-donor MHC class II cytotoxic T lymphocyte activity at either 20 or 60 days after transplant. Furthermore, transplantation of bm12 skins on C57BL/6-congenic, Ig knock-out mice was associated with the development of a chronic rejection that was identical to that occurring in wild-type C57BL/6 animals, indicating that alloantibodies are not necessary in this model. CONCLUSIONS: (1) Skin grafts may undergo chronic rejection with the characteristic lesions of vasculopathy and fibrosis; (2) chronic rejection of MHC class II-disparate skins may occur in the absence of direct cytotoxic T lymphocyte activity or alloantibodies.

Animals↗