Degree Of Cellular Differentiation Research Articles

Prognostisch relevante Faktoren beim follikul�ren Schilddr�senkarzinom

The discussion of the prognosis of follicular thyroid carcinoma is controversial. To evaluate the factors which influence the prognosis we retrospectively analyzed our patients from 1. 1. 1964 to 31. 12. 1987. 76 patients with a follicular thyroid carcinoma were treated during this time. Factors influencing the prognosis were: (1) multiple tumor growth; (2) pT-classification; (3) vascular invasion; (4) tumor stage; (5) degree of cellular differentiation and (6) metastases. Because of the prognostic influence of multiple tumor growth and the slight prognostic influence of lymph node metastases we recommend a total thyroidectomy with neck dissection for follicular thyroid carcinoma.

Catabolic Regulation of the Expression of the Major Myelin Glycoprotein by Schwann Cells in Culture

Previous studies have suggested that neonatal Schwann cell cultures deprived of axonal contact do not express components of the myelin membrane, including the major myelin glycoprotein, P0. In contrast, Schwann cells from permanently transected, adult nerve exhibit continued biosynthesis of P0 after culture, suggesting that the ability to express the myelin glycoprotein may depend on the degree of cellular differentiation. To examine further the ability of Schwann cell cultures to express P0 as a function of age, we have performed precursor incorporation studies on endoneurial explants from 4- to 12-day-old rat sciatic nerves after 5 days in culture. The data reveal that explants from 12-day-old animals synthesize detectable levels of this integral myelin protein when assayed by [3H]mannose incorporation, even though there is no apparent myelin assembly in the cultures. Pulse-chase analysis of cultures from 12-day-old rats demonstrates that [3H]mannose-labeled P0 is substantially degraded within 3 h. This catabolism largely can be prevented by the addition of swainsonine, ammonium chloride, or L-methionine methyl ester to the pulse-chase media. The former agent alters oligosaccharide processing whereas the latter two compounds inhibit lysosomal function. The P0 synthesized by the 12-day explant cultures following the addition of swainsonine is readily fucosylated, implying that the protein has progressed at least as far as the medial Golgi before its exit and subsequent catabolism. If cultures from 4-, 6-, and 8-day-old animals are analyzed for P0 biosynthesis by [3H]mannose incorporation in the presence of swainsonine, detectable levels of the glycoprotein are seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Histopathologic features of hepatocellular carcinoma in Zaire

The pathology of hepatocellular carcinoma (HCC) was studied based on 223 Zairian HCC cases registered from 1966 to 1985. The observations included the following: (1) hepatitis B surface antigen (HBsAg) status, (2) histologic types, (3) degree of cellular differentiation, and (4) frequency and types of the accompanying cirrhosis. Serum HBsAg was positive in 56.7% of HCC patients and 5.7% of controls (P less than 0.001). Immunohistochemical localization of HBsAg was positive in 53.3% in normal hepatocytes and in 10% in neoplastic cells. Morphologically, mixed type HCC (48.4%), trabecular (31.4%), and compact variants (13.5%) were predominant. Clear cell and pseudoglandular variants were rare (less than 1%). The majority of tumors (83%) were poorly differentiated HCC (Grades: 2-3, 3, 3-4, and 4). Well-differentiated HCC were extremely rare (0.5%). Fifty percent of HCC arose in a cirrhotic liver, predominantly of the macronodular (67.4%) inactive (55%) type. The micronodular cirrhosis was very uncommon (1.1%). These findings clearly show the excess of poorly differentiated HCC in African patients and suggest a possible link between the morphologic features of HCC in Africa and its extraordinary fast-running course.

Characterization of muscarinic acetylcholine receptors on intact neuroblastoma � glioma NG108-15 cell upon induced differentiation

Studies have established that major increases in muscarinic acetylcholine receptor (mAchR) binding in the brain appear to coincide with synaptogenesis. The neuroblastoma x glioma hybrid NG108-15 cell line has been demonstrated to possess numerous functional characteristics of intact neurons, including synapse formation with myotubes. The present study examines and characterizes the mAchR on the hybrid NG108-15 cells during differentiation, induced by 1 mM dBcAMP. Specific binding of [3H]-QNB for differentiated cells increases gradually to a final level of 130% (P less than 0.05) over the control undifferentiated cells during the first 24 hr of incubation. Further, this increase of receptor sites appears to correlate proportionately to the degree of neurite extension of the differentiating cells. The dissociation rate constant at equilibrium (Kd) and maximum binding capacity (Bmax) have been determined to be 5.6 nM and 920 fmol/10(6) cells, respectively, for differentiated cells, and 4.4 nM and 400 fmol/10(6) cells, respectively, for undifferentiated cells. Computer analyses of the data obtained from saturation experiments reveal a single class of binding sites for [3H]-QNB on both differentiated and undifferentiated cells. The Hill plot analysis of the QNB-binding indicates a Hill coefficient (nH) of 1.0 and 0.91 for differentiated and undifferentiated cells, respectively, suggesting the unity of receptor sites with no co-operativity. Our results depict that increases of mAchRs on intact cells correlate with the degree of cellular differentiation.

Amplification of the c-myc proto-oncogene in cervical carcinoma.

Amplification without structural rearrangements of the c-myc proto-oncogene was found in 14 of 44 primary cervical neoplasms. There was no apparent correlation with stage of disease or degree of cellular differentiation. The prognostic significance of c-myc amplification cannot be determined from this study.

Cell type-specific expressions of c-ras gene products in the normal rat.

Expression of proteins encoded by the ras proto-oncogenes was examined immunohistochemically in formalin-fixed, paraffin-embedded tissues of the normal rat using anti-ras p21 antibodies generated against synthetic peptides. Cell type specific expressions of ras gene products were detected in distal tubules of kidney, megakaryocytes in spleen, neural cells in cerebrum, Purkinje cells in cerebellum, cells lining the pulmonary alveoli and cells in the epithelium of intestinal villi. Region specific expressions of the ras proteins were observed in spleen and thymus, where the ras proteins were detected in splenic nodules including germinal centers and thymic medulla, respectively. These findings suggest that the c-ras gene products in normal rat organs are expressed in specific cell-types within a tissue and may be associated with degree of cellular differentiation.

Vitamin A and β-Carotene Concentrations at Different Depths of the Epidermis: A Preliminary Study in the Cow Snout

Vitamin A (retinol) is an anti-keratinizing agent essential for normal epithelial differentiation. In order to examine the epidermal distribution of vitamin A and provitamin A (beta-carotene), we took advantage of the extraordinarily thick snout epidermis of the cow which can be cut horizontally into at least 6 layers, representing keratinocytes at different stages of maturation. Extracts of saponified samples were analyzed for retinol and beta-carotene by reversed phase high-performance liquid chromatography. The highest retinol concentration (0.8 micrograms/g protein; n = 3) was recorded closest to the dermis; progressively decreasing amounts of retinol were found in the upper parts of epidermis. Maximum values of beta-carotene (1.0 micrograms/g; n = 7) were found in the lower parts of epidermis; substantially lower levels were seen at the dermal transition zone and in the upper parts of epidermis. The results suggest that the endogenous concentration of vitamin A in snout epidermis is inversely related to the degree of cellular differentiation.

Neuroblastoma: Report on a 21-Year Experience

This is a review of 80 patients with neuroblastoma managed at the American University of Beirut Medical Center between 1963 and 1983. Three patients had ganglioneuroblastoma of whom one showed histologic evidence of maturation into a ganglioneuroma. Four patients were less than 1 month of age and 33 were less than 2 years of age. The site of origin was intra-abdominal in 56 patients of whom 34 were intra-adrenal. Intraspinal involvement was noted in 12 patients, of whom one was a newborn. Treatment and adequate follow-up were possible in 63 patients. Total excision of the tumor was performed in 17 patients, and partial excision in 14. The 2-year and 5-year survival rates were 36% and 25%, respectively. Age, site of the tumor, and degree of cellular differentiation were the only independent variables affecting survival. Eleven of 14 patients younger than 1 year were alive 5 or more years after diagnosis. Cervical, thoracic, and pelvic tumors had a better prognosis than abdominal tumors. Other factors affecting survival were the stage and the mode of therapy. Infants with stage IV-S congenital neuroblastoma had a very poor prognosis. The initial urinary VMA level as well as the presence or absence of calcifications within the tumor had no bearing on prognosis.

Neuroblastoma: Report on a 21-year experience

This is a review of 80 patients with neuroblastoma managed at the American University of Beirut Medical Center between 1963 and 1983. Three patients had ganglioneuroblastoma of whom one showed histologic evidence of maturation into a ganglioneuroma. Four patients were less than 1 month of age and 33 were less than 2 years of age. The site of origin was intra-abdominal in 56 patients of whom 34 were intra-adrenal. Intraspinal involvement was noted in 12 patients, of whom one was a newborn. Treatment and adequate follow-up were possible in 63 patients. Total excision of the tumor was performed in 17 patients, and partial excision in 14. The 2-year and 5-year survival rates were 36% and 25%, respectively. Age, site of the tumor, and degree of cellular differentiation were the only independent variables affecting survival. Eleven of 14 patients younger than 1 year were alive 5 or more years after diagnosis. Cervical, thoracic, and pelvic tumors had a better prognosis than abdominal tumors. Other factors affecting survival were the stage and the mode of therapy. Infants with stage IV-S congenital neuroblastoma had a very poor prognosis. The initial urinary VMA level as well as the presence or absence of calcifications within the tumor had no bearing on prognosis.

Immunocytochemical evidence for neuroendocrine differentiation in human breast carcinomas.

Normal and neoplastic human breast tissues have been stained with antibodies recognizing neuroendrocrine differentiation. Fifteen out of 44 (34 per cent), breast carcinomas stained positively with monoclonal antibody LICRLON-E36, and 11 out of 44 (25 per cent) of these tumours stained with an antibody raised against neuron-specific enolase (NSE). Eight tumours stained positively with both antibodies. No correlation was observed between staining with these antibodies and the tumour histology, nor with the degree of cellular differentiation as indicated by staining with several cell surface directed monoclonal antibodies. Ultrastructural analysis of a series of breast tumours showed the presence of membrane-bound dense-core vesicles in almost all tumours, including E36 and NSE positive and negative tumours. The presence of these structures appears to be of little value in predicting neuroendocrine differentiation.

Pancreatic cancer. Assessment of prognosis by clinical presentation.

Three hundred ninety-three patients who were entered into pancreatic carcinoma treatment protocols of the Gastrointestinal Tumor Study Group (GITSG) were analyzed as to significant differences in clinical presentation and factors influencing survival. Patients were grouped according to the stage of the disease. Group I (21 cases) included those patients who had a potentially curative resection. Group II (182 cases) patients had a locally unresectable tumor less then 400 cm2 (surgically proven) and no distant metastases, and Group III (190 cases) had advanced disease. Group I patients had the smallest lesions (median area, 9 cm2), located in head of the gland in 90% and painless jaundice was the most frequent clinical presentation (52%). In Group II, 83% were located in the head of the gland but the median area was much larger (36 cm2). Pain was present in 80% of cases, and jaundice in 62% with 48% having jaundice and pain. In Group III patients, lesions of body and tail were over four-fold as frequent as in Group I and almost three-fold greater than in Group II. The median area of the lesion was large (30 cm2). Pain was present in 85% and jaundice in only 31%. Median survival in Group I patients was longer than Group III (73 versus 10 weeks; P less than 0.001). Ambulatory status, sex, race, abdominal pain, and histologic type influenced survival in one or more groups whereas age, jaundice, location of the tumor, degree of cellular differentiation, back pain, and nutritional status did not influence survival in any group. In all groups, those with a good performance status (Eastern Cooperative Oncology Group [ECOG] 0 and 1) survived longer than those with poor status (ECOG 2 and 3; P less than 0.05). The best potential prognosis is in those who are fully productive and present with painless jaundice, and who have resection of the tumor.

Lectin-binding patterns in the developing tooth

The lectin-binding patterns of the cells involved in amelogenesis and dentinogenesis in developing teeth of rats were studied. Undifferentiated odontogenic epithelia exhibited very slight staining with almost all of the lectins examined. The lectin-staining affinities of secretory ameloblasts could be divided into two categories: Concanavalin-A (Con-A), Wheat germ agglutinin (WGA) and Soybean agglutinin (SBA) binding occurred from the middle to apical cytoplasm, whereas Ricinus communis agglutinin-I (RCA-I) and Ulex europeus I (UEA-I) binding predominated in the basal regions. The cells of the stratum intermedium exhibited relatively strange lectin staining, which appeared to be dependent on ameloblastic maturation. The basement membranes in undifferentiated epithelia were markedly positive for lectin binding. Odontoblasts showed moderate Con-A staining on the apical side of the cells, as well as slight-to-moderate reactions with WGA and SBA. Pulp cells and dental papillae showed slight-to-moderate lectin staining, and predentin and dentin were also moderately positive for Con-A and RCA-I binding and slightly so for WGA and SBA. The lectin-binding affinities were enhanced during the formation of enamel and dentin, and appeared to be dependent on the degree of cellular differentiation in ameloblasts and odontoblasts.

Acinic cell carcinoma arising in the glossopalatine glands: A report of two cases with electron microscopic observations

Two cases of acinic cell carcinoma arising in the glossopalatine glands were examined with the electron microscope by means of conventional thin sectioning and freeze-fracturing. Light and electron microscopic observation revealed that the tumors consisted of three types of cells: serous-type, ductlike, and vacuolated cells. Serous-type cells had numerous secretory granules, some of which were discharged into the intercellular spaces. Ductlike cells were smaller, usually lacked secretory granules, and were similar to intercalated duct cells. Vacuolated cells had electron-opaque vacuoles in the cytoplasm. Our findings supported the hypothesis that acinic cell carcinoma may represent a neoplasm of multipotential duct cells which have differentiated mainly into granulated serous cells. Freeze-fracture images of this tumor revealed that tight junctions were composed of ten or more interlinked strands with elongation of basal frontier strands. These findings suggested that the junctional morphology of the tumor resembled that of developing salivary glands and was associated with the degree of cellular differentiation.

Carcinoma of the Endometrium

In a pathologic review of 1224 cases of endometrial carcinoma, 1023 were confirmed cases of endometrial carcinoma. Fifty-six (5.5%) were clear-cell adenocarcinoma (CCE). Fifteen cases of secretory (SCE) were examined for comparison. Fifty-five patients with CCE and all with SCE were followed for at least five years or until death. There were only 19 survivors among those with CCE. No five-year survivor subsequently died of disease. Of the 15 patients with SCE, 13 survived for five years although two additional patients died of recurrent disease at 5.4 and seven years. All survivors of CCE were Stage I patients at the time of diagnosis. All were postmenopausal, and had a median age of 67 years compared with 58 years for patients with SCE. Unlike SCE, the morphology of CCE was preserved in the subsequent hysterectomy specimen, in the recurrent disease, and in the metastases. CCE was proportionately more common in black women and the five-year survival was 12.5% as compared with 39.1% for white women. In contrast to endometrial carcinoma in general, most women who failed treatment died of disease. There was no increase in the relative frequency over the 23-year time period of the study. Age at time of diagnosis seemed to be an important prognosticator. Prognosis also correlated well with stage of disease and depth of myometrial invasion. It correlated to a somewhat lesser extent with the method of treatment and had a poor correlation with the histologic pattern or degree of cellular differentiation: however, essentially all tumors were considered to be poorly differentiated. Finally, a histologic tissue marker in the form of hyalin-like, PAS-positive, diastase-resistant bodies was found in the 64% of the women with CCE.

Lack of correlation between metastasis of human rectal carcinoma and the absence of stromal fibronectin.

In a retrospective study we have used an immunoperoxidase procedure to localize the glycoprotein fibronectin in human rectal carcinomas, concentrating on tumour invading thick-walled extramural veins. Fibronectin was present in 29 out of 38 cases, in connective tissue stroma, and was not in direct association with the tumour cells, except in areas of necrosis. We found no correlation between the presence or absence of stromal fibronectin and (1) the degree of cellular differentiation within the tumour, (2) tumour progression (Dukes' classification) (3) the subsequent development of metastases and (4) patient longevity. OUr results do not support the conclusions from in vitro studies (Smith et al., 1979) that the metastatic potential of carcinomas may be partly determined by the ability of tumour cells to synthesize pericellular fibronectin.

Immunohistochemical analysis of thyroglobulin and keratin in benign and malignant thyroid tumours.

56 thyroid gland tumours and non neoplastic alterations were studied for keratin and thyroglobulin staining, using the indirect immunoperoxidase method on serial formalin fixed paraffin embedded sections. Papillary carcinomas showed a strong reaction with anti-keratin serum but a weak reaction with anti-thyroglobulin serum. Follicular adenomas and carcinomas showed virtually no reaction for keratin but a strong reaction for thyroglobulin. Undifferentiated and medullary carcinomas did not react with either antiserum, except for single cells in two undifferentiated carcinomas which reacted with anti-keratin serum. In nodular goiters, hyperplastic follicles showed little or no reaction with anti-keratin serum and strong reaction with anti-thyroglobulin serum. It is suggested that this virtually type-specific staining for keratin or thyroglobulin may be related to different degrees of cellular differentiation and organelle content in the tumour cells.

The presence and distribution of glycogen particles in chondrogenic cells of the tibiotarsal anlage of developing chick embryos.

The distribution and localization of glycogen particles in mesenchymal cells, chondroblasts and in young, hypertrophic and degenerating chondrocytes of the tibiotarsal anlage of developing chick embryos were examined ultrastructurally using the periodic acid--thiocarbohydrazide--silver proteinate. The distribution of glycogen particles increased with the degree of differentiation and maturation of the chondrogenic cells. Mesenchymal cells showed minimal content of glycogen particles which gradually increased in the chondroblasts. The young chondrocytes further showed increased glycogen particle content compared to chondroblasts. This content reached a maximum level in hypertrophic chondrocytes. This level subsided in degenerating chondrocytes which showed a much reduced distribution of glycogen particles compared to hypertrophic chondrocytes. The morphological nature of glycogen particles depended on the degree of cellular differentiation. Both mesenchymal cells and chondroblasts contained single particles, while the glycogen particles of chondrocytes aggregated and formed a series of interconnected particles.

Serum alpha-fetoprotein and resection of primary hepatic cancer.

Alpha-fetoprotein (AFP) level was measured in five cases of hepatoma before and after hepatic lobectomy in order to determine if changes in AFP level were indicative of tumor residual or recurrence. It was felt that if this relationship could be proved, an elevation of AFP level might serve not only as a guide for detecting tumor, but as an indication for reoperation or chemotherapy or both. This study did demonstrate a relationship between the production of AFP and the histological type of hepatoma and its degree of cellular differentiation. The AFP value was also found to be correlated with the size of the tumor.

Control of hepatic fructose-metabolizing enzymes: fructokinase, aldolase and triokinase.

Abstract. Physiological factors which may regulate the catalytic activity of three key enzymes of hepatic fructose metabolism, fructokinase, aldolase and triokinase, are reviewed. Possible relationships between these potential control mechanisms and hepatic fructose metabolism per se are discussed at three distinct levels: 1) characterization in vitro of purified enzyme preparations; 2) variation of enzyme activity in vivo under various dietary and hormonal conditions; and 3) variation of enzyme activity in vivo following development of liver tumors of different growth rate and degree of cellular differentiation.

The Accuracy of Clinical vs Surgical Staging

Treatment of bladder cancer presents a serious and often perplexing problem to the urologist. From five different modes of surgical treatment and a minimum of three techniques of radiation therapy, he must select one which is suitable for the general condition of the patient having a bladder cancer of specific stage of infiltration, specific cell type, degree of cellular differentiation, size, and location within the bladder; and he must consider whether there are single or multiple lesions. Some of these factors have greater weight than others in determining the type of treatment and curability. The stage of infiltration of the bladder wall with a malignancy is, without doubt, the single most important factor. Many characteristics associated with infiltration and spread of tumor cells within the bladder have been observed and reported. Certain of these will be discussed subsequently as they apply to clinical, surgical, and histologic staging. Data concerning staging