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B R Rao

Publications and source records attributed to B R Rao.

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Subpopulations of breast carcinoma defined by S-phase fraction, morphology, and estrogen receptor content.

The S-phase fraction (SPF), defined as the number of cells per hundred that showed evidence of nuclear DNA synthesis detectable by autoradiography after in vitro incubation with tritiated thymidine, was measured in 170 primary, invasive carcinomas of the breast. Assay for estrogen receptor was performed on tissue from 129 carcinomas, and 34 were also assayed for progesterone receptor. The concentration of estradiol-17 beta was measured in the serum of 69 patients. All carcinomas were analyzed for a variety of histologic features and were classified into morphologic types. SPF were lognormally distributed and were negatively correlated with the patient's age and presence of estrogen receptor, but not with presence of progesterone receptor, size of the carcinoma, number of axillary nodal metastases, or concentration of estradiol-17 beta in serum. The SPFs of lobular, mucinous, and tubular carcinomas were consistently low (geometric mean 1.2, range 0.05 to 3.55), and the SPFs of medullary and atypical medullary carcinomas were consistently high (geometric mean 14.0, range 7.77 to 20.2), whereas carcinomas of other types (not otherwise specified) had an intermediate geometric mean (4.7) and a broad range (0.09 to 25.4). The carcinomas that were not otherwise specified could be divided into three groups with different geometric mean SPFs by nuclear morphologic criteria (1.2 for minimal atypicality, 3.5 for moderate, and 7.9 for severe). Therefore it is possible to sort breast carcinomas histologically into groups with low, intermediate, and high SPF. Correlations between SPF, estrogen receptor content, and microscopic morphology indicate the existence of distinctive subpopulations of breast carcinoma that may have epidemiologic and therapeutic importance.

Adenocarcinoma, Mucinous

S-phase fractions of breast carcinomas. Relationships to morphology, estrogen and progesterone receptors, and early recurrence.

Analysis of the S-phase fractions (SPF) measured by in vitro thymidine labeling, morphological appearances, and estrogen receptor (ER) assays of primary invasive breast carcinomas demonstrated several interrelationships. Lobular, mucinous, tubular, and adenocystic carcinomas consistently had low SPF and were usually positive for ER. The same was true for the carcinomas of no special histologic type [the not otherwise specified (NOS) group of E. R. Fisher including "infiltrating ductal" and undifferentiated carcinomas] with minimal anaplasia. Medullary, atypical medullary, and morphologically unclassifiable carcinomas with marked nuclear anaplasia nearly always had high SPF and were usually negative for ER. High SPF was associated with advanced stages of carcinoma initially or with early recurrence following mastectomy.

Anaplasia

Progesterone receptor in cystosarcoma phyllodes.

A specific receptor for progesterone has been found in a cystosarcoma phyllodes, as determined by charcoal adsorption and sucrose gradient analysis. Similar assays for estrogen receptors were negative. The tumor consisted almost entirely of stroma that contained the progesterone receptors. The epidemiology and natural history of cystosarcoma do not strongly support the hypothesis that it is controlled by female sex hormones, but the presence of the progesterone receptors suggests that some cystosarcomas are hormonally regulated, and thus may be responsive to therapeutic hormonal manipulation.

Aged

Low incidence of estrogen receptor in breast carcinomas with rapid rates of cellular replication.

The results of assay for estrogen receptor (ER) in the tumor cytosol and thymidine labeling indices (TLI) of 63 primary invasive carcinomas of the breast were analyzed. The ER assay was performed by using dextran-charcoal to adsorb unbound tritiated estradiol-17beta (E2) in cytosol. The TLI was measured as the number per hundred of neoplastic cell nuclei labeled by tritiated thymidine. A significant association between low TLI and presence of ER was found. Wereas all 19 tumors with TLI less than 2.5 contained ER in the primary lesion or in axillary metastases and ER was found in 25 of 30 tumors with TLI between 2.5 and 10, only 4 of 14 tumors with TLI greater 10 contained ER (p less than 0.001). TLI and saturable binding of E2 were significantly negatively correlated (r=-0.436,P. less than 0.001). It is concluded that dedifferentiation in breast carcinomas is associated with both high TLI and absence of ER, and suggested that the carcinomas with the most rapid proliferative rates will include the highest proportion of tumors unresponsive to hormonal therapy.

Adult