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Biomedical subjects

Antonio Cardesa

Publications and source records attributed to Antonio Cardesa.

18 recordsLinked to original sources

Power Doppler sonography of invasive breast carcinoma: does tumor vascularization contribute to prediction of axillary status?

PURPOSE: To prospectively compare unenhanced power Doppler sonographic findings of arterial vascularization of invasive breast carcinoma with histopathologic and immunohistochemical parameters and to determine whether tumor arterial vascularization contributes to prediction of axillary node status. MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. A total of 97 invasive breast carcinomas were prospectively studied with unenhanced power Doppler sonography before surgery. Lumpectomy or mastectomy with full axillary nodal dissection was performed. Sonographic tumor size and number of tumor arteries were correlated with axillary nodal status by means of logistic regression analysis. Tumor microvascularization was immunohistochemically assessed in a subset of 55 carcinomas. Sonographic variables were correlated with tumor arteries with a diameter larger than 300 mum and with the density and area of microvascularization. The kappa statistic and Bland-Altman agreement limits were used to measure agreement between techniques. RESULTS: Good agreement of sonographic and histologic findings regarding number of tumor arteries (kappa= 0.66, P < .001) and tumor size (P = .012) was observed. Multivariate analysis showed an independent relationship between probability of axillary metastasis, number of tumor arteries (P = .016), and sonographic tumor size (P = .035). A predictive model of axillary status was developed. The receiver operating characteristic curve was used to determine 0.2324 as the score to classify axillary nodal status. This score indicated high sensitivity (96.1%), low specificity (53.0%), and high negative predictive value (96.1%). CONCLUSION: The number of arteries in invasive breast carcinoma detected with unenhanced power Doppler sonography and sonographic tumor size are independent predictors of axillary nodal status; these variables could contribute to reliable prediction of absence of axillary involvement on the basis of a mathematic model.

Adult↗

Immunohistochemical staining for p16 and p53 in premalignant and malignant epithelial lesions of the vulva.

Two distinct types of vulvar squamous cell carcinomas and their precursors, vulvar intraepithelial neoplasias (VIN), which differ in terms of clinical presentation and behavior, have been delineated. Human papillomavirus (HPV)-associated carcinomas are of basaloid or warty type, whereas tumors unrelated to HPV are usually keratinizing and differentiated. Thus, the major stratifying factor for vulvar carcinomas and VIN is their etiopathogenetic relationship with HPV. However, because of technical difficulties in confidently detecting HPV in tissues, this diagnosis is usually based on purely morphologic criteria, even though some overlap exists between these histologic types. Recently, the tumor suppressor protein p16 has been shown to be specifically overexpressed in HPV-related carcinomas and premalignant lesions of the uterine cervix, oral cavity, and anus, but the presence of p16 vulvar squamous lesions has not been examined. We have evaluated the immunohistochemical expression of p16 in a series of formalin-fixed, paraffin-embedded vulvar carcinomas and their putative precursors. p16 was strongly positive in all cases of basaloid/condylomatous VIN3 (30/30) and basaloid (7/7) and warty (3/3) carcinomas. In contrast, p16 was almost consistently negative in normal skin, squamous cell hyperplasia (0/20), lichen sclerosus (0/19), differentiated (simplex) VIN3 (0/11), verrucous carcinoma (0/2), and keratinizing squamous cell carcinoma (3/33, 9%). One of the keratinizing squamous cell carcinomas positive for p16 occurred in a 25-year-old woman and the other two were associated with small foci of basaloid VIN3 adjacent to the tumor, suggesting a probable relationship with HPV. p16 was positive in 6 of 10 of basal cell carcinomas. In conclusion, p16 immunostaining is a good discriminator between HPV-associated and HPV-unrelated vulvar carcinomas and VIN, although it cannot differentiate basaloid squamous and basal cell carcinoma.

Adolescent↗

[Contribution of high risk human papillomavirus testing to the management of premalignant and malignant lesions of the uterine cervix].

BACKGROUND AND OBJECTIVE: High risk human papillomaviruses (HR-HPV) are consistently associated with premalignant and malignant lesions of the uterine cervix. Thus, the use of molecular techniques to detect HPV has been proposed to improve the results of conventional diagnostic strategies. In the present study, we evaluated the usefulness of the detection of HR-HPV in a cervical pathology unit. PATIENTS AND METHOD: 1005 women (mean age [SD], 38.4 [12.3]; range, 16-83) were referred for a cytology of atypical cells of unknown origin (ASCUS), squamous intraepithelial lesion (SIL) or carcinoma in the six months previous to the admission. All patients underwent a colposcopy, Pap test and/or histological study as well as HR-HPV detection using the Hybrid Capture II test. RESULTS: HR-HPV was detected in 96% high grade-SIL, 86% carcinomas of the uterine cervix and 86% low grade-SIL, but only in 25% women with no cervical lesions and 0% women with metastatic carcinomas to the cervix (p<0.001). The sensitivity of this test for high grade-SIL or higher was 90.2% and the negative predictive value was 96.5% (odds ratio=18.9; 95% confidence interval, 10.9-33.1). In patients with ASCUS, a negative result for HR-HPV nearly excluded the presence of a cervical lesion (negative predictive value, 98.52%). CONCLUSIONS: HR-HPV detection using Hybrid Capture II is useful in the study of lesions of the uterine cervix. It displays a high sensitivity for the diagnosis of squamous intraepithelial lesions and invasive carcinomas and a high usefulness in the management of ASCUS cases.

Adult↗

Carcinoma of the fallopian tube presenting as acute pelvic inflammatory disease.

BACKGROUND: Primary carcinomas of the fallopian tube are rare and their preoperative diagnosis is difficult due to the lack of specific symptoms. CASES: We present two tumors diagnosed in women 74 and 77 years old. On examination both patients presented as acute pelvic peritonitis with abdominal pain and tenderness with guarding and rebound, as well as fever and leukocytosis. At surgery, a left tubal carcinoma was found in each patient. Marked inflammatory and purulent reaction involving the uterus, the adnexa, and the pelvic peritoneum, and no abnormalities in the digestive tract were identified. A total hysterectomy with bilateral salpingo-oophorectomy was performed in both patients. CONCLUSION: Carcinoma of the fallopian tube should be considered in the differential diagnosis of pelvic peritonitis, a previously poorly reported clinical presentation.

Acute Disease↗

Endometrial pinopode and alphavbeta3 integrin expression is not impaired in infertile patients with endometriosis.

PURPOSE: To investigate endometrial receptivity in terms of pinopode formation and alphavbeta3 integrin expression in infertile women with endometriosis during natural cycles. METHODS: We investigated the expression of alphavbeta3 integrin and pinopode formation in the endometrium of 12 infertile patients with stage I or II endometriosis as the only cause of infertility, 12 infertile patients having unexplained infertility, and 12 fertile women who were undergoing tubal sterilization. Two endometrial biopsies (postovulatory day +7 to +8 and 4 days later) were performed during a single menstrual cycle in each subject. RESULTS: No statistically significant difference regarding alphavbeta3 integrin expression and pinopode formation was found between infertile patients with endometriosis and the two control groups. CONCLUSION: alphavbeta3 integrin expression and pinopode formation are not reduced during the window of implantation in patients with stage I-II endometriosis. Whether these results imply normal endometrial receptivity in such patients or add to the increasing uncertainty about the clinical value of assessing the endometrium with those markers of implantation, warrants further studies.

Adult↗

The effect of different hormone therapies on integrin expression and pinopode formation in the human endometrium: a controlled study.

BACKGROUND: Integrin expression and pinopode formation have been proposed as a means of distinguishing receptive endometrium from non-receptive in clinical practice, thus offering new directions for the development of contraceptive approaches targeted to the endometrium as well as a better understanding of occult causes of infertility in women. The aim of the present study was to investigate the effect of ovulation induction, oral contraception, treatment with dehydrogesterone, and different regimens of hormone replacement therapy on endometrial alphavbeta3 integrin expression and pinopode formation using a prospective, controlled study design. METHODS: Histological dating, alphavbeta3 integrin expression and pinopode formation were evaluated in control and treated cycles in six groups of women including eight subjects per group and who received clomiphene citrate, ovarian stimulation for IVF, oral contraception, dehydrogesterone for endometrial luteal phase defect, or two different regimens of hormone replacement therapy. Twelve healthy fertile women served as a general control group. RESULTS: Alphavbeta3 integrin expression and pinopode formation in the human endometrium were closely related to endometrial maturation as defined by histological dating and this was irrespective of endometria being in-phase or out-of-phase and the hormonal treatment received. Only for clomiphene citrate did a direct effect with reduction in pinopode formation in the midluteal phase seem to exist. CONCLUSION: Alphavbeta3 integrin expression and pinopode formation in the human endometrium are processes closely related to endometrial maturation and this is irrespective of endometria being in-phase or out-of-phase and the hormonal treatment received. The potential usefulness of those two so-called endometrial markers of implantation as targets for contraceptive approaches or fertility-promoting strategies seems unlikely.

Adult↗

CD10 expression in epithelial tissues and tumors of the gynecologic tract: a useful marker in the diagnosis of mesonephric, trophoblastic, and clear cell tumors.

We tested 417 cases of formalin-fixed, paraffin-embedded normal or hyperplastic gynecologic tissues as well as neoplasms involving the gynecologic tract with a monoclonal antibody against CD10 (clone 56C6), with special emphasis on epithelial and epithelial-like structures and tumors. CD10 was always expressed in mesonephric remnants (mesonephric remnants of the uterine cervix, epoophoron, rete ovarii) and tumors (mesonephric adenocarcinoma of the uterine cervix, tumors of wolffian origin of the broad ligament and ovary). CD10 was also positive in the syncytiotrophoblast, cytotrophoblast, and intermediate trophoblast of normal gestations, partial and complete moles, choriocarcinoma, and placental site trophoblastic tumors. Finally, CD10 was positive in several metastatic neoplasms to the gynecologic tract (100% in metastatic renal clear cell and intestinal carcinomas and melanomas). In contrast, CD10 was almost invariably negative in müllerian epithelia of the female genital tract and in their corresponding tumors, with the exception of focal expression found in squamous epithelia and tumors with squamous differentiation. Thus, the expression of CD10 may be useful in the establishing the diagnosis of mesonephric and trophoblastic tumors and in the differential diagnosis between gynecologic clear cell carcinoma (always negative) and metastatic clear cell carcinoma of renal origin.

Adenocarcinoma, Clear Cell↗

Within-subject between-cycle variability of histological dating, alpha v beta 3 integrin expression, and pinopod formation in the human endometrium.

alpha v beta 3 integrin expression and pinopod formation have been proposed as a means of distinguishing receptive endometrium from nonreceptive in clinical practice. However, one of the most intriguing facts in infertility is whether one cyclic event may be representative of all patients' cycles, and no study has evaluated the cycle-to-cycle variability of the expression of any of these new proposed markers in human endometrium. We investigated histological dating, alpha v beta 3 integrin expression, and pinopod formation in 45 endometrial biopsy specimens obtained in 15 primary infertility patients. All patients underwent three endometrial biopsies in consecutive spontaneous cycles, regardless of the previous histological findings. All endometrial samples were obtained on postovulatory d 7 as determined by ultrasonography. Agreement between the repeated observations (first vs. second, and first vs. third biopsies) with regard to histological dating and the presence or absence of alpha v beta 3 integrin and pinopods in the endometrium was analyzed using the 2 x 2 frequency tables and Cohen's kappa coefficient. The kappa values ranged from a low of -0.39 (level of agreement, poor) for alpha v beta 3 integrin expression to a high of 0.32 (level of agreement, fair) for biopsy dating by anticipated window of implantation. Overall, these results demonstrate that all endometrial variables investigated had poor reproducibility and high variability cycle to cycle.

Biopsy↗

Molecular biology of laryngeal squamous cell carcinoma.

Some of the mechanisms involved in neoplastic transformation and progression of laryngeal squamous cell carcinoma (LSCC) are discussed. Although tumor suppressor inactivation of p53 and p16 is common in these tumors (about 50% each), oncogenic activation is less well characterized. Cyclin D1 and epidermal growth factor receptor amplification have been reported in one-third and one-quarter of LSCCs, respectively, both related to advanced stages, whereas c-myc could be amplified in 13% of cases although without associated overexpression. The role of ras in LSCC is, at most, exceptional, and the role of human papillomavirus infection in these neoplasms could have been largely overestimated. The AIS (amplified in squamous carcinoma) gene has been recently proposed as the main oncogenic target in head and neck squamous carcinomas and is a promising line of investigation. This, along with the link that exists between p53 and INK4 suppressor pathways through ARF and MDM-2, and the role of the universal cdk inhibitors (the Cip/Kip family) in these neoplasms deserve further investigation. Not forgotten are the mechanisms leading to cell immortalization and invasive capabilities acquisition, some of which are also briefly described.

Carcinoma, Squamous Cell↗

Parotid gland mucoepidermoid carcinoma in a 4-year-old child.

Salivary gland tumors account for less than 5% of the head and neck neoplasms. Among them, mucoepidermoid carcinoma is the most common malignant salivary gland tumor. About 45% of mucoepidermoid carcinomas occur in the parotid gland, and appear around the fifth decade of life, being unusual in children under 10 years. We report a case of a parotid mass arising in a 4-year-old female, who had no lateral adenopathy. After histological examination, the diagnosis was of a low-grade mucoepidermoid carcinoma of the parotid gland. Three years after surgery no recurrence was observed. As a conclusion, although rare, the presence of a parotid mass with progressive growth in children could correspond to a neoplasm.

Carcinoma, Mucoepidermoid↗

ATM gene inactivation in mantle cell lymphoma mainly occurs by truncating mutations and missense mutations involving the phosphatidylinositol-3 kinase domain and is associated with increasing numbers of chromosomal imbalances.

The ataxia-telangiectasia mutated (ATM) gene codifies for a protein critically involved in the cellular response to DNA damage. ATM alterations have been observed in some sporadic lymphoproliferative disorders. The recurrent 11q22-23 deletions found in mantle cell lymphoma (MCL) suggest that ATM could be inactivated in these lymphomas. In this study, ATM gene alterations and protein expression were examined in 20 and 17 MCL tumor specimens, respectively. Previously, these patients had been examined for p53 and p14(ARF) gene status and analyzed by comparative genomic hybridization. Nine patients had 11q22-23 losses. Eight ATM gene mutations were detected in 7 patients. These alterations were 3 missense mutations in the phosphatidylinositol-3 kinase (PI-3K) domain and 5 truncating mutations, including 3 frameshifts, a nonsense mutation, and a substitution of the initial methionine. All truncating mutations were associated with lack of protein expression. Somatic origin was demonstrated in 3 mutations, whereas one mutation was carried heterozygously in the patient germ line. Chromosomal imbalances were significantly higher in typical MCL with ATM inactivation (7.8 +/- 1.3) than in tumors with the wild-type gene (3 +/- 1.1) (P =.001). Moreover, tumors with bi-allelic ATM alteration were associated with 3q gains (P =.015) and frequent extranodal involvement (P =.049). ATM gene alterations were not related to the histologic variant of the tumors, p53/p14(ARF) gene status, survival, or other clinicopathologic features of the patients. These findings indicate that ATM gene mutations in MCL are mainly truncating or missense mutations involving the PI-3K domain, and that may play a role in the pathogenesis of a subset of these tumors with increased numbers of chromosomal imbalances.

Alleles↗

Presence of occult cytomegalovirus infection in the brain after orthotopic liver transplantation. An autopsy study of 83 cases.

Cytomegalovirus (CMV) infection remains a highly prevalent systemic complication following orthotopic liver transplantation (LT), accounting for a significant increase in morbidity and affiliated costs. However, unlike other immunosuppressed groups of population, CMV infection of the central nervous system in LT is rarely diagnosed, either clinically or postmortem. Furthermore, in 20% of the LT patients who develop preterminal neurological complications, the etiology remains undetermined. With the hypothesis that at least some of these cases could be related to an occult CMV infection, we examined brain tissue from 83 unselected autopsies of LT patients by morphological, immunohistochemical (IHC), in situ hybridization (ISH), and nested polymerase chain reaction (nested PCR) techniques. Microglial nodules were observed in 17 brains of the LT group (20.4%) but in none of the 36 controls. Isolated positive cells by either IHC, ISH, or both techniques, were identified in 11 LT patients (13.2%) and in 2 controls (5.5%). CMV DNA amplification was obtained from paraffin-embedded tissues in 41 of 81 LT cases (50.6%), and in 5 controls (13.8%) (P=0.00017). Viral inclusion bodies, inflammatory infiltrates, or necrotizing changes were not identified in any case. Our findings indicate an increased susceptibility of the brain of LT patients to occult infection by CMV and suggest that a latent or low-grade infection of the central nervous system could operate as a reservoir of the CMV and play a role in some of the unexplained neurological symptoms that appear in the postoperative period.

Adolescent↗

Alterations of cell cycle-regulatory genes in prostate cancer.

Deregulated proliferation is one of the main events in neoplastic transformation, and this has prompted increased attention being given to the understanding of the mechanisms involved in cell cycle regulation and its alterations. The 'retinoblastoma pathway', a key effector controlling G1-S phase transition, includes several oncogenes and tumour suppressor genes which display a wide range of abnormalities with potential usefulness as markers of evolution or treatment response in prostate cancer. Among these, the existence of p53 mutations seems to predict resistance to radiotherapy or systemic treatment, and p16 overexpression or p27 downregulation seems to serve as markers of poor evolution. The well-established existence of a critical hormonal role in prostate carcinogenesis coupled with the relationship of androgenic activity and regulation of several cell cycle modulators forces cell cycle control in the prostate to be envisioned as a highly complex steroid-influenced system, which will undoubtedly have critical implications in the future management of prostate cancer patients.

Carcinoma↗

Ultrastructural and molecular heterogeneity in non-small cell lung carcinomas: study of 110 cases and review of the literature.

The authors reviewed a series of 110 surgical specimens of primary non-small cell lung carcinomas from the Department of Pathology at the Hospital Clinic, University of Barcelona Medical School, between 1987 and 1997. The sample included 25 squamous cell carcinomas, 60 adenocarcinomas, 14 large cell carcinomas, and 11 neuroendocrine tumors. Electron microscopic subcellular characteristics of the lung cancer cells were studied to define the squamous, adenoid, or neuroendocrine differentiation in each tumor. An immunohistochemical study for Cyclin D1 was performed in 96 cases. In 71 cases (65%) the author found a single ultrastructural differentiation, and in 30 cases (27%) ultrastructural differentiation was double: 25 adenosquamous and 5 adeno-neuroendocrine. In 3 cases a triple adeno-squamous-neuroendocrine differentiation was found. There were no cases of squamous-neuroendocrine differentiation. In 6 cases no differentiation of any kind could be found. Cyclin D1 overexpression was found in 58% of all tumors. The positive expression rates in squamous cell carcinoma and adenocarcinoma were 72% and 62%, respectively. In purely adenoid-differentiated tumors there was a strong association between high Cyclin D1 overexpression and differentiation (p=.006). In bronchioloalveolar carcinoma the positivity rate was 70%; all were heavy expressers, compared with 25% of heavy expressers in adenocarcinomas as a whole (p<.005). In purely squamous tumors differentiated ultrastructurally no relationship was found between high Cyclin D1 expression and degree of differentiation (p=.08). Lung cancers are morphologically and molecularly heterogeneous, and certain molecular alterations are related to specific subcellular characteristics.

Carcinoma, Non-Small-Cell Lung↗

Intranuclear inclusions in fine needle aspirates of bronchial low grade mucoepidermoid carcinoma with clear cell change: a report of two cases.

BACKGROUND: Mucoepidermoid carcinoma of the bronchus is a rare neoplasm that can be recognized on histology as well as cytology by the presence of three characteristic cell types: mucus secreting, epidermoid and intermediate. We encountered two cases displaying unusual cytologic features, including clear intranuclear inclusions. CASES: Two females, aged 33 and 39, presented with an intrabronchial tumor and pulmonary parenchymatous mass, respectively. Fine needle aspiration of both tumors showed similar cytologic features, with a dominant population of cells with bland nuclei and wide cytoplasm, and frequent intranuclear inclusions. A minor component of mucus-secreting cells was also recognized. Histologically, both tumors corresponded to the clear cell variant of mucoepidermoid carcinoma. CONCLUSION: The cytologic picture in our cases has not been described previously in fine needle aspirates of mucoepidermoid carcinoma, in neither the bronchus nor salivary gland. The differential diagnosis of a monotonous population of epithelial cells with intranuclear inclusions involves bronchioloalveolar carcinoma, but the absence of the characteristic sheet pattern, as well as the clinical and image findings, excludes this possibility. The lack of atypia and intrabronchial location limits the scope to carcinoid and salivary gland-type tumors of the bronchus. Since we were aware of the possibility of unusual cytologic presentations of mucoepidermoid carcinomas, search for different cellular populations suggested the precise diagnosis.

Adult↗

Low p27 expression predicts biochemical relapse after radical prostatectomy in patients with clinically localised prostate cancer.

OBJECTIVE: To assess the prognostic value of p27 protein expression in clinically localised prostate cancer with respect to biochemical recurrence after radical prostatectomy. PATIENTS AND METHODS: Fifty-two patients (median age 63 years) with prostate cancer were treated by radical prostatectomy in an 18-month period. Data recorded: preoperative PSA level, histopathological Gleason grade, pathological stage and status of surgical margins. p27 expression was evaluated in this group of tumors by immunohistochemistry (positivity was defined as > or = 30% positive cells). Biochemical relapse (BR) was defined by a serum PSA level > or = 0.3 ng/ml. RESULTS: Twenty-two out of 47 patients (47%) with available follow-up showed a low p27 protein expression. p27 expression did not correlate with pathological stage, Gleason score, serum PSA levels or the status of the surgical margins. Patients presented with BR during the follow-up (risk of BR (RBR) at 36 months: 40%). Patients with low p27 expression showed a higher RBR than the others (RBR 36-month 59% vs. 18%, respectively; p = 0.02). In a multivariate analysis, only p27 along with stage maintained the predictive value for biochemical relapse. CONCLUSION: p27 expression is a promising prognostic factor in prostate cancer, since it has proved to be a predictor of biochemical relapse.

Aged↗