Somatostatin receptor expression profile as a potential criterion for discrimination between seminoma and non-seminoma testicular tumors.

The expression of five (sst1-sst5) somatostatin (SRIF) receptor mRNAs was compared between normal and tumoral testicular samples diagnosed as either seminoma or non-seminoma. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis indicated that all testicular tissues studied (total of 24) contained sst5 receptor transcripts, whereas the sst2 was absent in all of them. In contrast to the normal tissue samples, both types of tumors (total of 12) did not contain sst4 transcripts. sst3 mRNA was expressed in normal and non-seminoma samples, but not in seminomas. sst1 transcripts were not found in normal and seminoma tissues. However, all studied non-seminomas contained this mRNA. Our data thus points to a specific pattern of SRIF receptor mRNA expression in each type of the samples analyzed. Moreover, they further indicate that the presence of sst1 and sst3 transcripts might be used as an additional criterion to distinguish between seminoma and nonseminoma tumors.

Medullary thyroid microcarcinoma: a clinicopathologic retrospective study of 38 patients with no prior familial disease.

Thirty-eight patients (25 women, 13 men; mean age, 57.8 [32 to 91]) showing one or more medullary thyroid microcarcinomas (ie, < 1 cm), with no prior MEN II or medullary thyroid carcinoma history in their family, were reviewed. Follow-up was available for 29 patients (mean, 53.6 months [1 to 147]). 21 patients (72.4%) are alive and free of disease, four patients (13.8%) died during follow-up without disease, 2 patients are alive with disease (local recurrence and persistent hypercalcitoninemia) after 80 and 99 months, respectively, and 2 patients died of disease after 24 and 46 months. Most tumors were incidental pathological findings (19 of 38) or were discovered by systematic blood calcitonin measurement for a nodular thyroid disease (15 of 38). Only the four patients who had an unfavorable outcome were symptomatic cases (palpable micro-MTC, diarrhea, cervical lymph node metastasis and pulmonary metastatic disease). The two patients with metastatic disease at diagnosis died during follow-up. In univariate analysis, a symptomatic medullary thyroid carcinoma was a strong predictor of an unfavourable outcome (p < .00008), as were the preoperative calcitonin level (P = .007) and an elevated postoperative calcitonin level (P = .004). Among 30 histopathological criteria, only the presence of amyloid correlated with an unfavorable outcome (P = .018).

Medullary thyroid carcinoma: search for histological predictors of survival (109 proband cases analysis).

A group of 13 pathologists belonging to the French Calcitonin Tumor Study Group (GETC: Groupe d'Etude des Tumeurs à Calcitonine) examined the histological slides and medical records of 109 proband cases of medullary thyroid carcinoma (MTC) diagnosed on clinical features. The cases belonged to the various forms of the disease (80 sporadic and 29 familial MTC). The aim of the study was to detect histological predictors for survival by comparing morphological data from patients killed by the disease versus the others. Twenty-seven histological parameters were considered, including cellular heterogeneity, shape of the cells, and cytoplasmic characteristics. Other parameters such as sex, age, and phenotype of the disease were also studied. First, predictive parameters of interest on survival function were selected by univariate analysis (Mantel-Cox test). Then, the extracted parameters were tested in a multifactorial analysis using the Cox's forward stepping proportional hazard model. Five parameters were significantly associated with a lower survival function: presence of necrosis in the tumor (P = .001), squamous pattern (P = .002), age over 45 years (P = .004), presence of oxyphil cells in the tumor and absence of cells with intermediate cytoplasm (P = .025), less than 50% of calcitonin immunoreactive cells in the tumor (P = .04).

Variability of Ha-ras (codon 12) proto-oncogene mutations in diverse thyroid cancers.

Structural alterations to proto-oncogene sequences may be involved in the pathogenesis of human thyroid neoplasms. We studied 128 thyroid tumours (35 benign and 93 malignant) for ras gene point mutations in three different codons (12, 13 and 61) using a restriction fragment length polymorphism technique and direct sequencing of double-stranded DNA on polymerase chain-reaction-amplified tumour DNA. We found a high frequency of ras mutation for the Ha-ras codon 12 in follicular adenomas (7 of 35), particularly in atypical adenomas (5 of 17), in follicular carcinomas (6 of 19), with a high percentage for Hurthle cell carcinomas (6 of 11), and in papillary carcinomas (4 of 66). Point mutations for other ras genes in different codons studied were weak to absent. No mutation was found in undifferentiated carcinomas (n = 8). The predominant amino acid substitution both in the adenomas and in the differentiated tumours was glycine to valine (GGC to GTC) at position 12 of the Ha-ras gene. Our results obtained on a large series confirm the frequent occurrence of Ha-ras codon 12 gene mutations both in adenomas and in carcinomas. The frequency of ras mutations is linked to the geographical origin of the population studied and varies (0-85%) from one cancer type to another according to published data. Therefore, these mutations are merely an expression of cellular transformation.

[Thyroid nodules: assay of serum thyrotropin and cytopuncture versus scintigraphy as first-line tests. Prospective study with 150 cases]. / Nodules thyroïdiens: dosage d'hormone thyréotrope sérique et cytoponction versus scintigraphie comme examens de première intention. Etude prospective sur 150 observations.

OBJECTIVE: Fine-needle aspiration (FNA) is now considered as the first-line investigation for the diagnosis of thyroid nodules. We searched for a more accurate and cost-effective methodology as this technique fails to recognized hot nodules, frequent in certain countries. PATIENTS AND METHODS: A prospective study was conducted in 150 patients to compare two diagnostic procedures: scintigraphy first combined with FNA in case of cold nodules versus TSH measurement plus FNA when TSH measurement plus FNA when TSH was not depressed. The results were subjected to cost/benefit analysis. RESULTS: Cystic nodules were found in 28 cases (including 3 hyperfunctionning nodules, with 5 suspicious smears (1 carcinoma). FNA was non-diagnostic in 26 patients; 12 were operated on (1 carcinoma), 14 had further FNA (5 suspicious, 9 benign). Altogether 56 nodules were removed, for toxic adenoma (n = 5), for suspicious (n = 21) or malignant (n = 12) smear, or on personal (n = 18) demand; 16 carcinomas were found (2 medullary, 13 capillary, 1 follicular carcinomas). With scintigraphy first, the cost was 787 French francs (FF) per patient. With TSH measurement and FNA, the cost was 554 FF per patient. In both cases, the same number of carcinomas were removed, and all the hot nodules (11 including 5 toxic adenomas) were detected. CONCLUSION: Serum TSH measurement, with scintigraphy if TSH is low, and FNA in all the other cases, is accurate and more cost-effective than scintigraphy as a first-line investigation for the diagnosis of thyroid nodule.

Androgen suppressive effect of GnRH agonist in ovarian hyperthecosis and virilizing tumours.

OBJECTIVE: Recent studies have suggested that androgen secretion by ovarian virilizing tumours may be gonadotrophin dependent. The aim of this study was to investigate the suppressive effect of GnRH agonist administration on androgen secretion in women with such tumours. DESIGN AND PATIENTS: A single i.m. injection of D-Trp-6-GnRH (GnRHa), 3.75 mg, was given to five unrelated patients referred for clinical symptoms of virilization with plasma testosterone (T) levels greater than 7 nmol/l but with normal dehydroepiandrosterone sulphate (DHEAS) levels. Diagnoses of adrenal tumour or a non-classical 21-hydroxylase deficiency were screened for by the dexamethasone suppression test, ACTH stimulation test and adrenal CT scanning, and were ruled out in all patients. The one premenopausal patient received cyproterone acetate in a dose of 50 mg twice daily for 3 weeks, starting 1 week before GnRHa administration. MEASUREMENT: Testosterone, androstenedione (A), DHEAS, 17-hydroxyprogesterone (OHP), LH and FSH plasma concentrations were measured by radioimmunoassay of blood samples taken before and 3 weeks after GnRHa. RESULTS: In each patient, GnRHa suppressed gonadotrophin levels and reduced T and A to the range for normal control women. With these results, and because accurate localization of an ovarian androgen secreting tumour could not be achieved by pelvic ultrasonography and CT scanning, exploratory laparotomy was undertaken. A Sertoli-Leydig cell tumour was found in the premenopausal patient, and granulosa cell tumour, hilus cell tumour and two hyperthecoses in the four post-menopausal patients. After bilateral ovariectomy and hysterectomy in the post-menopausal woman and after unilateral ovariectomy in the premenopausal women, androgen levels were normalized. CONCLUSIONS: In virilized women, the findings of increased serum testosterone with normal gonadotrophin levels and GnRHa suppression of gonadotrophins leading to normalization of testosterone levels, suggest that various ovarian androgen-secreting tumours, as well as hyperthecosis, are not autonomous but apparently depend upon continuous gonadotrophin stimulation.

Statistical analysis of histomorphological findings in medullary thyroid carcinoma: distinction between the different familial forms of the disease. G.E.T.C. Groupe d'Etude des Tumeurs a Calcitonine.

A multifactorial analysis of morphological findings was performed on 153 cases of medullary thyroid carcinoma (MTC). The aim of the study was to utilize histological criteria to discriminate between MTC associated with multiple endocrine neoplasia type 2A (MEN 2A) and that associated with the inherited MTC only syndrome. The presence of fusiform cells associated with several other markers seemed to be more predictive of MEN 2A. A comparison of inherited MTC only and sporadic MTC only showed fusiform cells to be significantly less common in inherited MTC only. These results suggest that the inherited MTC only syndrome is a distinct clinical and morphological entity. Further investigations are needed to confirm the findings and understand its implications.

The significance of the prostatic hypoechoic area: results in 226 ultrasonically guided prostatic biopsies.

A total of 666 patients with symptoms of urinary outflow obstruction underwent assessment of the patients 64 had a palpable abnormality suggestive of cancer (stages T1 to T4, or B to C). In the remainder the prostate was either palpably normal, firm or enlarged by benign prostatic hypertrophy. All 64 patients with a palpable abnormality and 162 of 602 with normal rectal examination findings had a hypoechoic area on transrectal ultrasound. Biopsy of the ultrasonic abnormality was done in 148 men by the transperineal route with linear array ultrasound guidance and in 78 by the transrectal route with a mechanical sector scanner in the sagittal plane. Of the 64 patients with a nodular prostate 34 (53%) had cancer (31% of those with stages T1 and 2, 83% with stage T3 and 100% with stage T4 disease). In 14% of the patients with stages T1 and T2 cancer the biopsy showed prostatic intraepithelial neoplasia grade 3. Of the 162 patients with a palpably normal prostate who underwent ultrasound-guided biopsy 11 (6.7%) had cancer and 6 (3.7%) had grade 3 prostatic intraepithelial neoplasia detected in the biopsy material. Patients with stages T1 to T2 cancer and those with ultrasound-diagnosed impalpable cancer were not significantly different with respect to patient age (67 versus 70 years), cancer size (3.0 +/- 1.6 versus 3.9 +/- 2.5 cm.2) or Gleason score (5.4 +/- 1.2 versus 6.5 +/- 0.9). The results demonstrate that ultrasound guidance improves the yield of prostate needle biopsy. Furthermore, it is suggested that prostate cancer found by ultrasound alone is not different from early palpable disease and should be treated in the same manner.

Flow cytometry analysis of leucocytes infiltrating bladder tumours according to grade and urothelial cell DNA content.

A series of 76 bladder tumours was studied using a panel of 5 anti-human leucocyte monoclonal antibodies (mAb): anti-pan-leucocytes (SLC1), anti-T lymphocytes (ST1), anti-B lymphocytes (SB3), anti-macrophages (PHM2) and anti-granulocytes (WEMG1). The DNA content and the expression for each mAb were measured in separate samples with flow cytometry. The importance of local inflammatory reaction was measured objectively according to tumour grade. These cells formed 41, 32 and 31% of the total cell count for grade I, II and III tumours respectively. The percentage of each leucocyte population according to grade I, II or III was as follows: 8, 5 and 6% respectively for T-lymphocytes; 3, 3 and 4% for B-lymphocytes; 10, 7 and 6% for granulocytes; 17, 18 and 24% for macrophages. No relationship was found between mAb expression and DNA content of tumours. This study demonstrates the importance of the inflammatory reaction in bladder tumours and the preponderance of cells expressing a macrophage phenotype. In a flow cytometry study, leucocytes may mask the presence of a minor group of urothelial tumour cells with an elevated DNA content associated with a poor prognosis; on the other hand, host leucocytes within a tumour could be used as an internal reference for precise measurement of the DNA content of tumour cells.

[Prognostic factors of differentiated thyroid cancers. 536 cases]. / Les éléments du pronostic des cancers thyroïdiens différenciés. 536 observations.

Five hundred thirty-six patients with papillary (n = 327) or follicular (n = 209) carcinoma of the thyroid treated between 1957 and 1985 in the same endocrine department are presented. Treatment was either an unilateral extracapsular lobectomy with isthmectomy, for isolated nodules only (n = 253), or a total thyroidectomy - with or without radio-iodine administration - or, exceptionally, a partial thyroidectomy. The impact of histologic type, age and sex of the patients, type of presentation and limited surgery (i.e. unilateral lobectomy in nodular carcinoma) were tested for prognostic value (total or relapse-free survival). The main factors are: initial tumour extension (almost no survival after 10 years in case of metastasis; 87.98 +/- 0.04% 20 years estimate of percent surviving in exclusive thyroid localization); histologic type (relative death rate: predominant papillary: 0.28, follicular well differentiated: 0.88, moderately differentiated: 2.54 (p less than 0.01); age (prognosis as better as the patient is younger); sex (worse prognosis for men above 40 years). Unilateral lobectomy is an unhazardous treatment with a survival rate 92.41 +/- 0.03% at 20 years for follicular and papillary nodular carcinoma.

Flow cytometric demonstration of shared antigens between human bladder cancer cells and normal host macrophages.

Leukocyte infiltration has been studied with flow cytometry in a series of 76 bladder tumors. Cell DNA content and surface immunofluorescence with a panel of 6 monoclonal antibodies (Mabs) were evaluated using a double-staining technique. The following Mabs were used: anti-CD5 (ST1); anti-CD37 (SB3); anti-granulocytes (WEMG1); anti-monocytes/macrophages (PHM2); a Mab directed against a bladder tumor-associated antigen (G4), and the anti-keratin-18 RGE53. Antigens recognized by Mabs ST1, SB3 and WEMG1, were only expressed by cells with a DNA index close to 1, whatever the grade or the DNA profile of the tumor. Conversely, PHM2 was not only expressed by cells with a DNA index close to 1, but also by cells with a DNA index of more than 1.5, i.e., by cells of the second peak in tumors with a bimodal DNA profile. Thus the PHM2 epitope was not exclusively expressed by macrophages but also by urothelial tumor cells with an elevated DNA index. A significant positive correlation (r = 0.87; p less than 0.01) was found between DNA index and PHM2 reactivity among cells of the second peak in tumors with a bimodal DNA profile, whereas there was no correlation between DNA index and cytokeratin-18 expression and a weak negative correlation (r = -0.42; p less than 0.02) between DNA index and G4 Mab reactivity. These findings support the hypothesis of a cell fusion between human malignant urothelial cells and normal host macrophages.

[Value of the prostatic puncture biopsy in the diagnosis of prostatic cancer. Apropos of 271 cases]. / Valeur de la ponction biopsie prostatique dans le diagnostic des cancers prostatiques. A propos de 271 observations.

271 patients have been submitted to prostatic needle biopsy between january 1973 and september 1984. Sensitivity and specificity of transperineal prostatic biopsy for prostatic carcinoma are respectively 89% and 98%. Complications are met in 10% of these cases. Rectal examination has been compared to these results. Sensitivity is 75% and specificity 70%. Prostatic biopsy appears to be a good method for diagnosis of prostatic carcinoma but less effective than fine needle aspiration for cytologic examination.

[Prognosis of the thyroid carcinomas after surgery (author's transl)]. / Pronostic des cancers thyroïdiens extra-capsulaires opérés.

The authors review 140 cases and show the prime importance of the patient's age and the histological type in the prognosis of the operations of thyroid carcinoma (with the exception of solitary malignant cold nodule). The survival rate is higher with the papillary carcinoma of young patients, even though an extensive development of lymph nodes occurs, whereas metastases are encountered in the evolution of follicular carcinoma with increased risks. The anaplastic carcinoma which occurs mainly in aged people, is the worst of all. The medullary carcinoma is quite different from the others and is almost as malignant as the differentiated and anaplastic carcinomas. Surgery has to be adapted to anatomical lesions and requires the presence of an experienced histopathologist, the extension of the gland excision depending on the histological type and whether the isthmic area has been touched or not; in the same way a microscopic examination of lymph nodes, which are systematically excised, reveals whether a lymph nodes dissection has to be done at the same time. In this way extensive excisions together with their sequels can be avoided when the best prognosis can be forecasted with these lesions.

[A prospective study of malignancy criteria in 407 surgical patients (author's transl)]. / Nodules froids thyroïdiens. Etude prospective des critères de malignité chez 407 malades opérés.

A prospective study of 407 patients with "cold" solitary thyroid nodule seen over 4 1/2 years and systematically operated upon was undertaken with the view of determining the pre-operative criteria of malignancy. Thirty-nine nodules were malignant. Since various methods of multidimensional statistical analysis failed to give satisfactory results, an attempt was made to base rational surgical indications on purely descriptive criteria. Neither the patient's age, morphology, personal or family history of thyroid disorders, nor the size of the nodule, the circumstances in which it was discovered and the presence of calcification made it possible to distinguish between malignant and non-malignant nodules. Cervical lymph node involvement, paralysis of the recurrent nerve, previous irradiation of the neck and site of the nodule equally had no discriminative value. Only two clinical findings, softness of the nodule and liquid content, were clearly associated with the absence of malignancy.