Biomedical subjects

B Tetu

Publications and source records attributed to B Tetu.

15 recordsLinked to original sources

PubMed2001

Does histologic grade have a role in the management of head and neck cancers?

PURPOSE: High histologic grade is usually associated with a greater propensity to distant metastases (DM). Its role to predict DM in head and neck cancer is not yet defined. The aim of this study is to evaluate the role of histologic grade as an independent predictor of DM and to determine a subgroup of patients who may benefit from systemic chemotherapy. PATIENTS AND METHODS: This is a retrospective study of 1,266 consecutive patients treated by definitive or postoperative radiotherapy between 1989 and 1997. All patients received at least 50 Gy. All stages and subsites of head/neck were included. DM rates were evaluated by the Kaplan-Meier method with a subsequent Cox analysis. RESULTS: There is a strong correlation of grade with N stage (P <.000001). The metastases-free survival (MFS) was 98%, 90%, and 72% for grades 1, 2, and 3, respectively (P <.000001). In patients with N0 stage, MFS is always greater than 90%, whatever the grade. In the 222 N1 patients, MFS was more than 90% in grade 1 and 2 but dropped to 75% for grade 3 (P =.001). In patients with N2 and N3, MFS was 91%, 79%, and 59% for grades 1, 2, and 3, respectively (P =.008). The same conclusion is applicable when only patients with neck control are analyzed. In a Cox model, grade was an independent predictor of DM (P =.000001) as well as T stage (P =.003), N stage (P =.000001), and neck failure (P =.0003). Higher grade was also an independent predictor of survival (P =.02). CONCLUSION: Patients with histologic grade 1 and grade 2 (except N3) are at low risk of DM. Patients with grade 2 and N3 or patients with grade 3 and N1 to N3 have a higher risk of distant metastases and should be considered for systemic treatment.

Aged↗

PubMed2000

Tumorigenic pathways in low-stage bladder cancer based on p53, MDM2 and p21 phenotypes.

Our aim was to determine whether the pattern of expression of the interrelated proteins p53, MDM2 and p21 could shed light on the etiopathogenic mechanisms of superficial bladder tumors. Protein expression was detected by immunohistochemistry (IHC) using monoclonal antibodies (MAbs) Pab 1801 for p53, IF2 for MDM2 and EA10 for p21 on 269 newly diagnosed bladder tumors (214 pTa and 55 pT1; 93 grade I, 145 grade 2 and 31 grade 3). While no p21 immunoreactivity was found in normal urothelium, 85% of tumors were strongly p21-positive. MDM2 was overexpressed in 44% of tumors, almost all being also positive for p21. p53 was overexpressed in 20% of cases: 66% of p53-positive tumors were also MDM2 positive, compared with only 38% of p53-negative tumors. p53 mutations were studied by direct DNA sequencing in a subset of 24 high-grade tumors. Both MDM2 and p21 were less frequently expressed in p53 mutated tumors compared with tumors with a wild-type gene. Distinct phenotypes were correlated with the frequency of poorly differentiated (grade 3) tumors. The most common phenotypes were p21+/MDM2-/p53- and p21+/MDM2+/p53- observed in 38% and 29% of tumors, respectively. Grade 3 tumors were found in 4% and 8% of these 2 groups, in contrast with 30% frequency in p21+/p53+ tumors (p = 0.002) regardless of their MDM2 phenotype. Four of the 5 (80%) tumors that were p53-positive but negative for p21 were grade 3. Our data suggest that several tumorigenic pathways for superficial bladder tumors can be reflected by the expression pattern of these 3 proteins.

Aged↗

PubMed1999

Persistence of high-grade prostatic intra-epithelial neoplasia under combined androgen blockade therapy.

The presence and morphology of high-grade prostatic intraepithelial neoplasia (H-PIN) was blindly evaluated in 40 totally embedded radical prostatectomy specimens of patients with prostate cancer randomized to either a 3 (n = 18) or 6 months (n = 22) combined androgen blockade regimen before surgery. In 5 cases, neo-adjuvant therapy was abrogated some time before surgery. In the remaining cases, foci of H-PIN were identified in 72% and 59% of prostates from patients treated for 3 and 6 months, respectively. Cellular features used to distinguish H-PIN from normal glands were increased nuclear size, nuclear crowding, anisonucleosis, and disordered nuclear arrangement. In some cases, density of cytoplasm was an additional feature. Unfortunately, the molecular marker erbB2 proved unhelpful for identification of H-PIN. The median number of prostatic glands involved by H-PIN was 19 +/- 21 (SD) glands in 3 months treated prostatectomies (n = 18) and 7 +/- 12 (SD) glands in 6 months treated prostatectomies (n = 17), a nonsignificant difference (P = .17). H-PIN was localized within areas of residual carcinoma in 62% and 20%, respectively of prostatectomies of patients treated for 3 and 6 months, respectively. Architectural patterns of H-PIN differed at 3 and 6 months of endocrine pretreatment: The predominant tufted pattern at 3 months was replaced by flat H-PIN at 6 months. The continued expression of androgen receptors and the cell cycle marker MIB-1 in persistent H-PIN suggests that recovery of androgen levels after cessation of androgen blockade therapy will lead to its further expansion.

Androgen Antagonists↗

PubMed1997

Neoadjuvant hormonal therapy: the Canadian experience.

OBJECTIVE: To assess the effect of neoadjuvant combination therapy with the antiandrogen flutamide and a luteinizing-hormone-releasing hormone (LHRH) agonist administered for 3 months before radical prostatectomy, compared with surgery alone in early stage prostate cancer on histopathologic findings at surgery and serum prostate-specific antigen (PSA). METHODS: A sample of 161 randomly screened patients diagnosed as having stage B (134 patients) or C (27 patients) prostate cancer were randomly assigned to radical prostatectomy alone or to 3 months of neoadjuvant combination therapy with the antiandrogen flutamide and an LHRH agonist before radical prostatectomy. RESULTS: Neoadjuvant combination therapy before radical prostatectomy decreased cancer-positive surgical margins from 33.8% in the control group to only 7.8%, thus leaving 92.2% of patients with negative margins at surgery. A net 54% improvement of staging was observed in favor of combination therapy. Organ-confined disease, on the other hand, increased from 49.3% to 77.8% of patients after 3 months of combination therapy, for a 57.8% increase in the incidence of organ-confined disease. No cancer was found in 6 (6.7%) prostatectomy specimens from the treated group. A close correlation was found between serum PSA at diagnosis and the stage of the disease at surgery. Upstaging increased from 30% at serum PSA values of 0 to 3.0 ng/mL up to 100% at serum PSA values above 15 ng/mL. CONCLUSIONS: Although long-term follow-up of these patients is required to determine the impact on survival, the marked influence of neoadjuvant combination therapy on the stage of the disease suggests the possibility of a major improvement in the morbidity and mortality from prostate cancer.

Adenocarcinoma↗

PubMed1996

Prevalence and clinical significance of HER/2neu, p53 and Rb expression in primary superficial bladder cancer.

PURPOSE: The usefulness of the expression of HER2/neu oncoprotein and of p53 and Rb suppressor gene product as predictors of tumor recurrence was evaluated by using a bank of prospectively collected primary papillary bladder tumors treated initially only by transurethral resection. MATERIALS AND METHODS: The expression of HER-2/neu oncoprotein and p53 and Rb suppressor genes was evaluated by immunohistochemistry in 256, 265 and 74 specimens of primary Ta/T1 superficial bladder tumors obtained from patients enrolled in a prospective study from 1990 to 1992. Survival analysis was used to evaluate the association between time to first recurrence and expression of each marker, the follow-up period extending to March 1994. Immunostaining for p53 and HER-2/neu was performed on paraffin-embedded tissue and, for Rb, on frozen tissue only. RESULTS: Her-2/neu was expressed in 21 (8.2%) cases and p53 in 39 cases (14.7%); Rb expression was altered in 12 (16.2%). In this study, p53 expression was only related to earlier recurrence in a univariate analysis. Multivariate analysis, however, failed to recognize p53 expression as an independent predictor of recurrence. CONCLUSIONS: Our study demonstrates the low prevalence of HER2/neu, p53 and altered Rb expression in superficial TCC at initial resection. Only p53 expression was significantly associated with an earlier first tumor recurrence, but this association was not independent of other prognostic factors.

Aged↗

PubMed1995

The molecular basis of Turcot's syndrome.

BACKGROUND: Turcot's syndrome is characterized clinically by the concurrence of a primary brain tumor and multiple colorectal adenomas. We attempted to define the syndrome at the molecular level. METHODS: Fourteen families with Turcot's syndrome identified in two registries and the family originally described by Turcot and colleagues were studied. Germ-line mutations in the adenomatous polyposis coli (APC) gene characteristic of familial adenomatous polyposis were evaluated, as well as DNA replication errors and germline mutations in nucleotide mismatch-repair genes characteristic of hereditary nonpolyposis colorectal cancer. In addition, a formal risk analysis for brain tumors in familial adenomatous polyposis was performed with a registry data base. RESULTS: Genetic abnormalities were identified in 13 of the 14 registry families. Germ-line APC mutations were detected in 10. The predominant brain tumor in these 10 families was medulloblastoma (11 of 14 patients, or 79 percent), and the relative risk of cerebellar medulloblastoma in patients with familial adenomatous polyposis was 92 times that in the general population (95 percent confidence interval, 29 to 269; P < 0.001). In contrast, the type of brain tumor in the other four families was glioblastoma multiforme. The glioblastomas and colorectal tumors in three of these families and in the original family studied by Turcot had replication errors characteristic of hereditary nonpolyposis colorectal cancer. In addition, germ-line mutations in the mismatch-repair genes hMLH1 or hPMS2 were found in two families. CONCLUSIONS: The association between brain tumors and multiple colorectal adenomas can result from two distinct types of germ-line defects: mutation of the APC gene or mutation of a mismatch-repair gene. Molecular diagnosis may contribute to the appropriate care of affected patients.

Adenomatous Polyposis Coli↗

PubMed1993

Granulosa cell tumor of the adult testis: a clinicopathologic study of seven cases and a review of the literature.

We report a study of seven men, aged 16 to 76 years (average age, 47.4 years) with granulosa cell tumor (GCT) of the testis. Three patients presented with testicular enlargement of several years' duration and a fourth presented with a testicular enlargement of unknown duration. The tumors in three patients were detected during routine physical examination. None of the patients had endocrine-related symptoms. All tumors were well circumscribed and showed the solid, cystic, microfollicular, gyriform, insular, and trabecular patterns typical of GCT of the ovary. Call-Exner bodies were present in three tumors and two tumors had a focal spindle-cell component. In one case the surrounding testicular parenchyma showed Leydig's cell hyperplasia and a Sertoli cell nodule. The tumor cells revealed strong immunoreactivity for vimentin but showed no expression for keratin or epithelial membrane antigen. One patient developed liver and retroperitoneal lymph node metastases 121 months after initial diagnosis and died 13 months later. Another patient initially presented with retroperitoneal lymph node metastasis and developed metastasis to the inguinal lymph nodes 12 months later. Three patients are alive at 1, 4, and 37 months with no evidence of disease. Another patient died of an unrelated condition. Follow-up information was not available for the seventh patient. Twelve cases of GCT of the adult testis have been reported in the literature, with metastases occurring in two: one of these two patients had a tumor for 8 years and died of disease 5 months after diagnosis with multiple metastases and the other had metastasis at the time of diagnosis, but was free of disease for 14 years. Our findings and a review of the literature indicate that GCT of the adult testis is a rare and slow-growing neoplasm with the potential to form distant metastases. Because recurrence or distant metastasis may occur late in the clinical course, long-term follow-up of these patients is recommended.

Adolescent↗

PubMed1991

Large cell calcifying Sertoli cell tumor of the testis. A clinicopathologic, immunohistochemical, and ultrastructural study of two cases.

The clinicopathologic, immunohistochemical, and electron microscopic study of two patients with large cell calcifying Sertoli cell tumors (LCCSCT) of the testis is reported to elucidate the histogenesis of this rare tumor. Both tumors occurred in young individuals (16 and 32 years); case 1 was found incidentally, and the patient in case 2 presented with a 3-4-week history of testicular pain. Evidence of testosterone production was demonstrated in one case. In the same case, at the ultrastructural level Charcot-Böttcher crystalloids were observed. These data support previous reports that LCCSCT shows Sertoli cell differentiation.

Adolescent↗

PubMed1990

Merkel cell carcinoma metastatic to the testis.

Tumor metastases to the testes are rare and are usually found incidentally at autopsy or after orchiectomy for prostatic carcinoma. It is even more unusual for testicular metastases to be clinically detected or symptomatic. The authors report two cases of clinically detected testicular metastases from Merkel cell carcinoma of the skin. Merkel cell carcinoma metastatic to the testes has not been reported previously. The two tumors, to some degree, resembled testicular lymphomas and the interstitial type of seminoma.

Aged↗

PubMed1988

Generation of monoclonal antibodies reactive with nuclear proteins of human primary breast tumors.

Nuclear proteins were extracted from purified nuclei of human primary breast tumors (BrT) and bladder tumors and of human normal breast, kidney and lymphocytes by enzymatic treatment. SDS-Polyacrylamide gel electrophoresis of nuclear proteins from breast tumors showed different bands in the molecular weight zones from 25 to 220 kDa which were absent or present only as traces in normal breast tissue. Murine monoclonal antibodies (MAbs) have been produced using nuclear extracts of human primary breast tumors as immunogens. Approximately 2,000 hybridomas were generated from 5 hybridizations. According to their reactivity to BrT nuclear extracts and mammary carcinoma cell line MCF-7, seven hybridomas were selected and cloned. They were further characterized with histological immunoperoxidase assays of formaldehyde-fixed BrT paraffin tissue sections. MAb 6A3 particularly gave strong nuclear staining with all BrT specimens while MAb 1D8 showed both nuclear and cytoplasmic staining with only some of them. Specimens from mammoplasty did not react with these MAbs. Immunoblotting of BrT nuclear extracts as developed with MAbs 6A3 and 1D8 revealed major protein bands with molecular weight of 120 and 130 kDa. The potential use of these MAb-defined BrT-related nuclear proteins as markers for human breast cancer was suggested.

Antibodies, Monoclonal↗

PubMed1987

Syncope and hypotension due to carcinoma of the breast metastatic to the carotid sinus.

Tumors involving the carotid sinus and glossopharyngeal nerve may produce syncope due to bradycardia and hypotension. Carotid sinus syncope unrelated to cancer is usually caused by bradycardia and responds to control of the heart rate. When neoplastic disease involves the carotid sinus, vasodepressor hypotension, with or without bradycardia, is more common. Control of the heart rate alone is not effective. Although this syndrome is not common, it is probably not recognized in milder forms. Most patients in whom this syndrome develops have cancer of the head and neck. A patient with breast carcinoma metastatic to the neck and carotid sinus is described in whom syncope with hypotension and bradycardia developed. Although a temporary cardiac pacemaker controlled bradycardia, severe hypotensive episodes recurred despite treatment with anticholinergic and sympathomimetic drugs. The pathophysiology and therapy of this syndrome in patients with cancer are reviewed.

Aged↗

PubMed1987

Squamous cell carcinoma of the ovary.

A 45-year-old woman developed a grade III and stage III squamous cell carcinoma of the left ovary 12 years after a hysterectomy for treatment of endometriosis. Origin from a teratoma or a Brenner tumor was excluded. Despite extensive surgery with additional radiation therapy and chemotherapy, the patient died five months after the malignancy was diagnosed. Squamous cell carcinoma of the ovary, either de novo or arising from endometriosis, has rarely been reported. We describe a case of ovarian squamous cell carcinoma in which endometriosis is strongly favored as the origin, but that remains speculative.

Carcinoma, Squamous Cell↗

PubMed1986

Sertoli-Leydig cell tumor of the ovary with alpha-fetoprotein production.

A case of poorly differentiated Sertoli-Leydig cell tumor with elevated serum alpha-fetoprotein (AFP) levels occurred in a 17-year-old girl. No germ cell component and no heterologous elements were identified, but a retiform pattern was present. Immunohistochemical studies demonstrated immunoreactivity for AFP and testosterone in Leydig's cells only. Secretion of AFP by Sertoli-Leydig cell tumors has rarely been mentioned previously, and its mechanism is difficult to explain. Non-germ cell tumors must be considered in the differential diagnosis of ovarian tumors with elevated serum AFP levels.

Adolescent↗

PubMedDate not supplied

[Renin-secreting renal tumor. Apropos of a case with an ultrastructural and immunohistochemical study].

A case of renin-secreting tumor of the left kidney in a 36 year-old man with hypertension of five years duration is reported. The antihypertensive therapy was unsuccessful. Following nephrectomy, blood pressure returned to normal values and is still normal, seven years later. There is no evidence of metastasis. The tumor was studied by electron microscopy and by immunohistochemistry. It is composed of two cellular structures normally encountered in the kidney: renin-secreting cells and cells similar to those of the cortical collecting ducts. This benign lesion might be hamartomatous.

Adult↗

PubMedDate not supplied

[Evaluation of the differences of opinion in the histopathologic diagnosis of soft tissue tumors].

Evaluation of observers variation in the histopathologic diagnosis of soft tissue tumors. 260 cases of soft tissue tumors referred to the CTRC (Canadian Tumour Reference Center) for diagnostic opinion were reviewed. These tumors were collected from 98 different hospitals within the 10 canadian provinces and had been submitted to a specialized panel of pathologists having a particular interest in this field. 22 tumors of nonmesenchymal origin have been discarded. The main problem posed by the contributors related to the histologic typing of overtly malignant and sarcomatous tumors (122/238). Comparing the diagnoses proposed by contributors and the panel, a consensus in term of benign and malignant tumor was reached in 89% of the cases. Within this panel, there was consensus in 84% of the cases. However, regarding the histologic typing, a consensus was reached between contributors and the panel in only 65% of the studied cases. Within the panel, there was a majority diagnosis in merely 62% of them. A mean of three different diagnoses were proposed for each case. A review of the literature shows that histologic typing of soft tissue tumors is of only limited prognostic significance. On the other hand, the clinical staging comprising histologic grade, size, depth, local growth and metastases is essential to establish prognosis and treatment. However, since certain tumors respond differently to treatment, a precise histopathologic diagnosis using immunohistochemistry and electron microscopy is mandatory.

Diagnosis, Differential↗