Anaplastic Forms Research Articles

COMMON PRECURSOR MOLECULE AS ORIGIN FOR THE ECTOPIC-HORMONE-PRODUCING-TUMOUR SYNDROME

When messenger R.N.A. (m-R.N.A.) extracted from various hormone-secreting tumours was injected into Xenopus eggs, the translation products in all cases proved to be a protein of molecular weight 65 000. Analysis by polyacrylamide-gel electrophoresis and specific precipitation reactions with antibodies showed a striking similarity between the various proteins. When translation products of m-R.N.A. from calcitonin-secreting medullary thryroid carcinoma (M.T.C.) and the non-secreting anaplastic form of M.T.C. were incubating with specific enzyme systems (the microsomal fraction) from both types of tumour, enzymes from anaplastic M.T.C. had no effect on the translation products, whereas enzymes from differentiated M.T.C. degraded the translation products from both differentiated and anaplastic M.T.C. These results support the hypothesis that the primary gene product of all the different types of carcinoma cell studied is a single large protein (a hormone precursor or prohormone) containing different specificities. The specific enzyme system in each carcinoma cell probably selects the specific hormone liberated from this primary protein.

Intermediate (10 nm)-Filaments in Undifferentiated Cells of Mouse Neuroblastoma Clones

Neuroblastoma cells, grown in monolayer, transform, emit cytoplasmic processes, and acquire morphological and functional properties resembling those of mature neurons, whereas in suspension culture they remain in the undifferentiated anaplastic form. The appearance of intermediate (10 nm) filamentous structures in neuroblastoma cells is generally considered to indicate a state of cellular differentiation, one of a progressive sequence of maturing phases which lead the cell to the final differentiated state. We have examined by electron microscope murine C 1300 neuroblastoma cloned cells, grown in suspension or in monolayer cultures in the presence or absence of BrdU as an inducing agent and have compared the expression of intermediate filaments. These filaments were present in five clones of cells grown in suspension still in undifferentiated anaplastic form. One clone in particular showed a massive expression of filaments, particularly visible in the perinuclear region. One hundred per cent of the cells observed presented filaments whose number apparently increased when cells were grown in the presence of BrdU in suspension or in monolayer. One clone never showed intermediate filaments under any circumstances. The original line from which clones were derived showed poor expression of filaments which were visible only in cells grown in monolayer. These results suggest that the expression of intermediate filaments in neuroblastoma cells should be viewed as the result of a positive genetic control of phenotype expression rather than the result of a progressive sequence of differentiating events.

PROGESTERONE BINDING IN HUMAN ENDOMETRIAL CARCINOMAS

Abstract By means of dextran-coated charcoal assay, the capacity of various endometrial cytosol preparations for specific binding of 3 H-progesterone was determined. With the use of an arbitrary value of 50 femtomoles of bound 3 H-progesterone per milligram of cytosol protein as the breaking point between high and low binding capacities, 19 out of 20 normal endometria had high progesterone-binding capacities. Two out of 11 Grade 1, 3 out of 8 Grade II, and 2 out of 4 Grade III endometrial carcinomas showed low binding capacities. All 4 endometrial polyps, 7 out of 9 hyperplastic endometria, and 0 out of 7 nonendometrial gynecologic tumors had high binding capacities. These data suggest a progressive loss of specific progesterone-binding activity from normal endometria to hyperplastic endometria, and from the well-differentiated to the anaplastic forms of endometrial adenocarcinoma. There seemed to be an inverse relationship between age and concentration of progesterone receptors in endometrial adenocarcinomas. All irradiated tumors studied had low progesterone-binding capacity.

An Anaplastic Form of “So-Called Inverted Papillary Tumor” of the Urinary Bladder, Associated With Poor Prognosis of the Patients

An Anaplastic Form of “So-Called Inverted Papillary Tumor” of the Urinary Bladder, Associated With Poor Prognosis of the Patients

Progesterone binding in human endometrial carcinomas

By means of dextran-coated charcoal assay, the capacity of various endometrial cytosol preparations for specific binding of 3H-progesterone was determined. With the use of an arbitrary value of 50 femtomoles of bound 3H-progesterone per milligram of cytosol protein as the breaking point between high and low binding capacities, 19 out of 20 normal endometria had high progesterone-binding capacities. Two out of 11 Grade 1, 3 out of 8 Grade II, and 2 out of 4 Grade III endometrial carcinomas showed low binding capacities. All 4 endometrial polyps, 7 out of 9 hyperplastic endometria, and 0 out of 7 nonendometrial gynecologic tumors had high binding capacities. These data suggest a progressive loss of specific progesterone-binding activity from normal endometria to hyperplastic endometria, and from the well-differentiated to the anaplastic forms of endometrial adenocarcinoma. There seemed to be an inverse relationship between age and concentration of progesterone receptors in endometrial adenocarcinomas. All irradiated tumors studied had low progesterone-binding capacity.

Volume VI: Tumors of the Thyroid Gland.

This volume is the best and most complete work on tumors of the thyroid gland that this reviewer has seen. The book begins with an historical review and describes statistical methods for studying the epidemiology of thyroid tumors. It is apparent that there has been very little change in the incidence of this dsease in the past several decades. The mortality figures again show that there is a low death rate from this disease, which is confined primarily to the anaplastic form of tumor. Its higher frequency in females is also emphasized. Two chapters on the present knowledge of the cause of thyroid tumors, written by I. Doniach, are probably the best chapters in the book, and deal beautifully with concepts of thyroid tumors' causation with particular reference to radiation and constant pituitary stimulation of the thyroid gland. One of these chapters is on experimental work and it emphasizes the

Pathologic Differentiation and Prognosis of Prostatic Carcinoma

The morphologic appearance of has been well described 8,53,54 and is generally considered noncontroversial; however, the histologic criteria for classification of this cancer according to degree of malignancy are not well understood and certainly not generally accepted. 55,56 The fact that cellular and structural variations from the benign to the most anaplastic forms of malignancy may be seen in a single microscopic section of a specimen accounts in part for this disagreement. The pathologist must decide whether the most representative cellular pattern or the area of greatest cellular anaplasia should be taken as indicative of the growth potential of the tumor. 57 Since it is generally agreed that adenofibromatous hyperplasia is not neoplastic, almost all prostate tumors are malignant. In common usage, prostatic carcinoma is synonymous with adenocarcinoma, since the latter accounts for about 97% of these tumors. The remaining tumors are the rare sarcomas and squamous

Can Radiosensitivity and Histopathology of Cervical Cancer Be Correlated?

The histopathology of cervical cancers can be correlated with the local radiocurability for (1) groups of cases and (2) the individual patient. The histological type of carcinoma influences the local radiocurability, since the five-year symptom-free survival rates are significantly better for cases with mature than for those with anaplastic carcinomas of the same clinical stage of the disease (Table 1). In addition to the series of 898 patients quoted in the introduction 3 a series of 1,633 cases 11 classified at the time of starting treatment between 1946 and 1953 gives very similar results. These figures show that (1) for the same clinical stage, differentiating (ie, mature) tumors are more amenable to radiotherapy than anaplastic cancers; (2) the incidence of mature types decreases and that of anaplastic forms increases with increasing clinical stage, ie, the latter account for 67% in stage I, 77% in stage II, and 85% in stages

Relationship of histology to prognosis in thyroid carcinoma

Prognosis in carcinoma of the thyroid varies more widely and consistently with the histologic pattern than perhaps any other neoplasm. This fact has been observed particularly in relation to the papillary forms, which have a good although not necessarily an excellent prognosis. The follicular form is associated with only a fair prognosis, and the anaplastic forms are invariably rapidly fatal. A major proportion of the differentiated carcinomas of the thyroid exhibit a mixed pattern of both papillary and follicular elements. The clinical implications of the respective roles of these two components in the mixed forms have not been emphasized by most studies of thyroid cancer. The usual classifications do not recognize the mixed forms as such, assigning given tumors to either papillary or follicular categories according to predominant cell type. In an effort to evaluate the clinical significance of predominance of either the papillary or follicular elements in the mixed

Relationship of Histology to Prognosis in Thyroid Carcinoma

Prognosis in carcinoma of the thyroid varies more widely and consistently with the histologic pattern than perhaps any other neoplasm. This fact has been observed particularly in relation to the papillary forms, which have a good although not necessarily an excellent prognosis. The follicular form is associated with only a fair prognosis, and the anaplastic forms are invariably rapidly fatal. A major proportion of the differentiated carcinomas of the thyroid exhibit a mixed pattern of both papillary and follicular elements. The clinical implications of the respective roles of these two components in the mixed forms have not been emphasized by most studies of thyroid cancer. The usual classifications do not recognize the mixed forms as such, assigning given tumors to either papillary or follicular categories according to predominant cell type. In an effort to evaluate the clinical significance of predominance of either the papillary or follicular elements in the mixed

The effect of radiation on ascites tumour cells.

Mouse ascites tumour cells, which grow freely suspended in the abdominal cavity of the animals, can be considered an anaplastic form in contrast to the more differentiated spindle cells from which they are derived. On explanation into tissue culture and on subcutaneous injection in vivo the free round cells become transformed into spindle cells. T2146 and S37 ascites tumour cells were exposed in vitro to γ radiation before and after establishment of the spindle forms in tissue culture and injected subcutaneously into C3H mice immediately after radiation. The radiation effect on the tissue cultures, as measured by the number of tumours obtained from irradiated grafts of cultures, was the same in both tumour strains and independent of whether the cells were exposed as round or spindle forms. Exposure to γ radiation in vitro of S37 ascites tumour cells and S37 spindle cells derived from subcutaneous tumours showed the former to be much more radiosensitive. The MLD was 500 r units for the ascites form and 2600 r units for the subcutaneous sarcoma. It is tentatively suggested that the great radiosensitivity of the ascites tumour cells may be related (1) to the fact that many of these cells do not reconstruct fully after mitosis and be due to an action of radiation similar to that seen on premitotic cells in other tissues, and (2) to their low metabolic activity.

Primary Sarcoma of the Stomach

THE stomach is a rare seat of the sarcomas, but they probably are more frequently present than recognized, because of the lack of characteristic clinical symptoms and roentgen diagnostic signs, and the fact that not every gastric tumor, surgically removed, undergoes microscopic study. Even the pathologist may misdiagnose a gastric sarcoma on account of its close resemblance to anaplastic (embryonal) forms of carcinoma (3) and other conditions more frequently found in gastric lesions. Freeman (7) reported a case of gastric sarcoma in which prominent pathologists gave a diagnosis of carcinoma, lymphosarcoma, inflammation, and chronic granuloma. The first gastric sarcoma was reported by Bruck, in 1847, and the first operation was performed by Virchow, in 1887. The frequency of gastric sarcoma is about 1 per cent of the malignant gastric conditions, as estimated by Ewing (6), Phillips and Kilgore (14). The ratio was 1 : 121 at the Mayo Clinic (1) during the period from 1908 to 1928. In 4,509 malignant gastric tumors operated upon in seven large clinics in various parts of the world, the sarcoma-carcinoma ratio was found to be 1 : 93. Only one gastric sarcoma has been reported in the Berlin Pathologic Institute (11) among 840 specimens of sarcomas. The age sector of gastric sarcoma is wider than that of carcinoma; there are cases on record in every decade of life up to the ninth. The extremes are Finlayson's three-and-one-half-year-old and Giacomma's ninety-one-year-old patient. The average age incidence is 43 years, at the Mayo Clinic (1); other reliable statistics state similar age incidence, the most frequent decade being the fourth (9). These data verify the appearance of gastric sarcoma earlier in life than that of carcinoma. Most of the statistics report an even distribution of cases in both sexes. At the Mayo Clinic, males are affected three times as frequently as females. Histologically, the gastric sarcomas are classified as fibro-, myo-, lympho-, and myxosarcoma. Fibrosarcoma originates in the submucosa; myosarcoma in the muscularis; lymphosarcoma in the lymph nodes of the submucosa; subserous origin of these sarcomas is less frequent (13). Clinically, they may be exo-, endogastric, and intramural tumors; well defined or diffuse growths. The exo- and endogastric types are sometimes pedunculated. Fibro- and myosarcoma arise mostly from the curvatures; pyloric involvement is rare. Brodowsky reported a tumor the size of a child's head; Cantwell, one weighing 12 pounds. Also exceedingly small tumors are described. Endogastric growths sometimes undergo ulceration and may cause severe, even fatal, hemorrhages. These tumors usually grow slowly, metastasize late, and form a well-defined mass.