[Epidemiologic and morphogenetic aspects of prostate cancer].
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Biomedical subjects
Publications and source records attributed to G Dhom.
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We investigated the utriculus prostaticus from the fetal period up to adulthood in 148 prostates. During the second half of gestation the utriculus had a simple tubular or a cystic form and was lined with metaplastic squamous epithelium which showed immunohistochemical positivity for different keratins, carcinoembryonic antigen, and peanut agglutinin binding sites. After birth, alveolar outgrowths of the utriculus developed. After puberty, the utriculus had become a complicated and variable structure. The epithelium no longer differed from that of the prostate glands either morphologically or immunohistochemically. Within the epithelium numerous endocrine cells were found containing neuron-specific enolase, chromogranin, and serotonin. The utriculus and ejaculatory ducts were embedded in a fibrous stroma with, after birth, numerous plexus-like blood vessels. This fibrous zone was peripherally bordered by a layer of smooth muscle. There was no evidence for a function of the utriculus differing from that of the prostate glands. Since the epithelium of both structures is identical immunohistochemically, the epithelium of the sinus urogenitalis most likely particpates in the lining of the utriculus during embryogenesis.
Over 90% of malignant epithelial tumors of the prostate are common carcinomas. Uncommon or rare prostate carcinomas can histogenetically be related to 4 epithelial types of the prostate: the secretory epithelium, the basal cells, the endocrine cells and the transitional epithelium. The rare, purely mucinous carcinoma and the ductal papillary carcinoma belong to the type of secretory epithelium. The latter is rarely seen in the large central prostatic ducts, it develops more frequently in peripheral ducts and is combined with common prostate carcinoma. The so-called endometrioid carcinomas of the utriculus described in the literature are probably ductal prostate carcinomas. To date no carcinoma has been found in the utriculus. The adenoid cystic carcinoma of the prostate is a basal cell tumor with preponderantly good prognosis. Endocrine cells are disseminated in most common prostate carcinomas. Thereby mixed forms showing both portions of a common adenocarcinoma and of a carcinoid may occur. Pure carcinoids of prostate are rare findings. The small cell carcinoma of the prostate is the highly malignant variant of the endocrine cell type. Immunohistochemically, a multitude of proteohormones are demonstrable in endocrine tumor cells. The ectopic ACTH production with Cushing's syndrome is of particular clinical significance.
Eleven case of squamous cell carcinoma of the prostate have been divided into four groups according to their histological features and natural history: a pure squamous cell carcinoma of the prostate (one case); b common prostatic adenocarcinoma with malignant squamous component after oestrogen treatment (two); c urothelial carcinoma of the prostate with malignant squamous cell metaplasia (four); and d urothelial carcinoma of the urinary bladder with squamous cell metaplasia growing into the prostate (four). The squamous portions may spread to invade the fibromuscular stroma and grow in prostatic ducts. Necrosis of comedo type and inflammatory infiltrates appeared in a number of cases. The survival times of nine patients ranged from 1 to 17 months. Squamous components were shown by immunohistochemistry to contain various keratin types, carcino-embryonic antigen and peanut agglutinin binding sites. Whenever a squamous cell carcinoma in the prostate is diagnosed histologically various possibilities as to its origin should be considered.
There is a network of hospital registries at cancer centers in the Federal Republic of Germany which, by 1985, had registered about 200,000 patients. Although the hospital registries do not have a strict population basis, the data obtained could be used for analytic epidemiological studies. The hospital registries are hindered from doing their own epidemiological cancer research mainly by their shortage of personnel. A particular organization - a pediatric cancer registry in Mainz - has registered about 95% of all childhood neoplasias and leukemias since 1980. Of the population-based registries of the Saarland, Hamburg, and Münster, only the Saarland Cancer Registry can at present provide actual incidence rates. In the three federal states of Saarland, Hamburg, and North Rhine-Westphalia, laws concerning cancer registries were enacted with different regulations regarding registration. In Hamburg and North Rhine-Westphalia the patient has to approve forwarding of his personal data to the registry. Exceptions are permitted under special conditions. Pathology institutes cannot report directly. In the Saarland, research institutes are not allowed to be given personal data. The position of the epidemiological cancer registries is actually threatened by the official application of restrictive data-protection laws.
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Estrogen (ER) and Progesterone receptors (PR) were demonstrated immunohistochemically on frozen sections from 11 prostatectomy and 7 cystoprostatectomy specimens in the nuclei of various cell types. The periglandular fibrocytes and smooth muscle cells were extensively positive, the interglandular stromal cells were only partly so. Normal basal cells stained focally positive, hyperplastic basal cells stained extensively. The glandular secretory epithelium and atrophic glands were negative. The same findings were obtained in hyperplastic nodules. Both ER and PR also occurred in the urothelium of central prostatic ducts and of the prostatic urethra. The fibrous stroma around the ejaculatory ducts and seminal vesicles was extensively positive while the epithelium was negative. The smooth musculature of the seminal vesicles was only partly positive. On large field sections, the ER as well as the PR were numerically equally distributed throughout the inner zone of the prostate and the prostate proper. 12 prostatic carcinomas (G I-G III) were ER- and PR-negative. Estrogens may contribute to nodular hyperplasia by triggering a stromal proliferation with a secondary inductive epithelial growth. Obviously they do not act directly on prostatic carcinoma but inhibit growth via the hypophyseal-testicular axis. The biological significance of the PR in the prostate is unknown.
Histopathologic diagnosis of prostate carcinoma is not yet free of problems. There are particular difficulties in demarcating atypical forms of hyperplasia from well-differentiated carcinomas and in diagnosing and classifying incidental carcinomas. With the aid of conventional histology, however, nearly all diagnostic problems relevant for the patient can be solved. In routine diagnostics, modern immunohistochemical techniques are particularly helpful in assessing metastases of an undetected primary tumor. New immunohistochemical techniques provide insight into the receptor content of the prostate and show the histogenesis of prostate carcinoma in a new light. The estrogen receptor (modified ER-ICA test) is present in the nuclei of stromal cells and of basal cells within the glands, but not in the secretory epithelium. The receptor-associated protein--ER-D5--is found in the cytoplasm of stromal and basal cells. In basal cells and secretory epithelium, keratins show a different pattern. Immunohistochemically common adenocarcinomas display the pattern of secretory epithelium; urothelial and squamous cell carcinomas, on the contrary, display the pattern of basal cells. This finding does not support the opinion that the basal cell is the stem cell of secretory epithelium and the precursor cell of prostate carcinoma.
Fifty carcinomas that were partially to completely papillary in nature were examined. According to urethroscopic and rectal palpation findings, six of the carcinomas were located centrally, 40 tumors were in the prostate proper, and four were clinical stage T0. The epithelium of the papillary portions of the tumors was dark in some instances, light in others. Immunohistochemistry revealed that 20 of 22 tumors were positive for prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA). In no case was a topical relationship to the utriculus prostaticus demonstrable. The epithelium of the utriculus in seven additional patients who were not involved in this series also stained positively for PAP and PSA. Usual carcinomas of the prostate proper can develop endometrioid structures that do not differ immunohistochemically from ordinary portions of the carcinoma. Tumors located in central portions of the prostate are, in our opinion, morphologic variants of usual prostatic carcinomas, and apparently arise in prostatic ducts. We conclude that a distinction between endometrioid carcinomas and tumors of prostatic ducts does not seem justified and that papillary prostatic carcinomas should be treated like common prostatic cancer.
Pre-operative staging of rectal cancer could be significantly improved by the imaging method of endorectal ultrasound. Using high-frequency transducers a complex rectal wall pattern was demonstrated. Depending on in vitro or in vivo examinations and on US probes of different frequency the current interpretation is not uniform. Agreement exists on the interpretation of the muscularis propria which is of clinical importance. Objective and precise criteria for lymph node differentiation have yet to be worked out.
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The present study is based on the data of 321 cases of primary liver cancer (PLC); 225 hepatocellular carcinomas (HCC), 54 cholangiocellular carcinomas (CCC) and 35 unclassified carcinomas autopsied between 1963 and 1982 or reported to the Saarland Cancer Registry between 1967 and 1981. The age standardized incidence rate for the Saarland was determined as 1.1. We noticed an increase in incidence for both HCC and CCC. The HCC rise was based on a significant (p less than 0.05) increase for women. The incidence maximum in the successive birth cohorts is shifting into younger age groups. The highest rates were observed in men and women born between 1900 and 1909. The regional distribution of PLC in the Saarland shows an accumulation in the urban areas. The mean survival time from diagnosis to death was 3.1 months. Prognosis was only influenced by the grade of differentiation. 88.3% of the HCC, but only 28.6% of CCC occurred in cirrhotic livers. Orcein staining of 55 liver specimens showed evidence of previous HBV infection in 12 out of 38 cases of HCC (31.6%) and no evidence of HBVB in the 17 cases of CCC studied.
The behaviour of keratins in the human prostate is investigated immunohistochemically by polyclonal rabbit antibodies against keratins from human stratum corneum (kit from ORTHO/Heidelberg) and compared to the behaviour of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA). In normal glands and cribriform as well as adenomatous hyperplasia only basal cells contain keratin. The secretory epithelium is keratin-negative and in contrast to the basal cells PAP- as well as PSA-positive. In prostatic ducts and utriculus prostaticus keratin is demonstrable in basal cells and urothelium. As in normal glands, the light cylindric epithelium is keratin-negative and PAP- as well as PSA-positive. The cells in atrophic glands and postatrophic hyperplasia may contain keratin as well as PAP and PSA. Urothelial and squamous metaplasia are strongly keratin-positive. PAP and PSA are not found. The cylindric epithelium of the ejaculatory ducts contains keratin at many places. PAP and PSA are not demonstrable. The utriculus does not differ from normal prostatic glands immunohistochemically. This supports the view that the epithelium of the sinus urogenitalis is involved in the embryogenesis of normal prostatic glands and the utriculus as well. Urothelial and squamous metaplasia obviously arise from basal cells which share the same immunohistochemical features. Whether the cells in atrophic glands and postatrophic hyperplasia derive from basal cells or secretory epithelium cannot be decided. The keratin composition of the prostate should be further analyzed by keratin-specific monoclonal antibodies.
Eight-week-old male and female Sprague Dawley rats are treated with 10 micrograms estradiol daily i.p. for 2 and 4 weeks respectively. Under treatment pituitary and adrenal weight increases in males and similates to those of females. As a relative measure for the cell sizes in the different zones of the adrenal cortex the number of nuclei/constant area is determined. In the outer zona fasciculata estradiol leads to a feminization of cell pattern in males with increase of cell sizes and partly also development of a female liposome pattern. An increase of cell sizes in the zona reticularis between the second and fourth week of treatment is restricted to male animals. In the zona glomerulosa cell sizes increase in males between the 10th and 12th week of life, independent of estradiol. In both sexes estradiol causes a significant dilatation of sinusoids of adrenal medulla. Most of the findings can be explained by known biochemical aspects of corticosterone metabolism of the rat.
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The frequency of malignancy grade I-III (grading system according to Böcking and Sommerkamp, 1980) and of clinical stages T0-T3 in 393 unselected prostatic carcinomas (227 punch biopsies and 166 transurethral resections) were investigated over a period of 2 years. G III carcinomas were represented most frequently in the whole material (54%) as well as in punch biopsies (62%). G I carcinomas with a favorable prognosis make up 20% of the tumors in the whole material and only 10% in punch biopsies. In contrast, 54.9% of incidental carcinomas (T0) are G I tumors, 18.6% G III carcinomas with an unfavorable prognosis. The advanced clinical stages T2 and T3 predominate in the whole material with 62.4%, compared to stages T0 and T1 comprising 37.6%. Malignancy grade and clinical stage are clearly correlated in the whole material. In incidental carcinoma, there is also a correlation between malignancy grade and histologic extension. The percentage of higher malignancy grades G II and G III increases with age. This is true for incidental carcinoma as well. The findings emphasize the prognostic significance of the grading system.