Shanthi Raam -United States Of America

Title DIRECTOR

TUFTS UNIVERSITY BOSTON

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Keywords

  • breast neoplasm, breast neoplasm /cancer diagnosis, neoplasm /cancer classification /staging DNA binding protein, antibody formation, estrogen receptor, hormone related neoplasm /cancer, human therapy evaluation, interferon, monoclonal antibody, neoplasm /cancer hormone therapy, neoplasm /cancer immunodiagnosis, neoplastic cell, postmenopause, progesterone receptor, surface antigen body fluid, female, histochemistry /cytochemistry, histopathology, immunofluorescence technique, laboratory rabbit, tissue /cell culture

Summary Information

  • Recipient of US government research funding (9)
    8,306,749
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    USA Grants

    IMMUNOHISTOCHEMICAL CLASSIFICATION OF HUMAN BREAST TUMOR
    (1992)

    Abstract :

    This proposal addresses the important issue of hormone therapy failures among post-menopausal women with estrogen receptor- positive ER(+) breast cancer with or without progesterone receptors (PR). Clinical correlation studies have shown that the current methods of sub-classification of ER(+) tumors based on the presence/absence of proteins which are markers of estrogen action (ex. PR) are inadequate for precise differentiation of truly hormone-responsive from hormone-resistant ER(+) tumors. The level of prediction error (30% ER+/PR+ failures and 25-30% ER+/PR- responders to hormone therapy) translates to significant proportions because 75% of 100,000 newly diagnosed cases of breast cancer will be ER(+) and 50-60% of these will be PR(+). A precise sub-classification of primary biopsies of ER(+) tumors will be valuable for early selection of potential hormone therapy failures when the tumor burden is small so that alternative therapies can be administered to benefit the patient. With the help of polyclonal antibodies (Pab) to ER, in-vitro hormone incubation procedure and immunohistochemistry (IF) developed in our lab we have identified two varieties of ER in human cancers which, although capable of binding estrogens with high affinity, are defective in their nuclear binding function. Preliminary clinical correlation data have also revealed a preponderance of these defective ER among those breast cancers which are hormone resistant and of non-defective ER among those which are responsive to hormone therapy. Based on these results and of previous investigations emphasizing a correlation between defective ER and hormone- independent growth WE PROPOSE THAT A SUB-CLASSIFICATION OF ER(+) TUMORS BASED ON NUCLEAR BINDING CHARACTERISTICS MAY DISCERN TRULY HORMONE-DEPENDENT TUMORS FROM RESISTANT ONES. Our SPECIFIC GOALS , therefore, are: (1) To develop novel monoclonal antibodies (Mabs) to identify and discriminate among the defective/non-defective ER based on their epitope differences; (2) To immunotype with Pabs and IF, the ER in established ER(+) human breast cancer cell lines with known hormone response data; (3) To attempt establishment of primary cultures from malignant fluids of patients with ER(+) tumors who failed hormone therapy and to immunotype ER with Pabs; (4) To immunotype sequential biopsies of ER(+) tumors (primary vs recurrent) to find out if recurrences become enriched in cells with defective ER; to increase patient population for clinical response to hormone therapy.


    Project Number : 5R01CA037944-06
    ICD : NATIONAL CANCER INSTITUTE
    IRG : EI
    Project Terms : breast neoplasm, breast neoplasm /cancer diagnosis, neoplasm /cancer classification /staging DNA binding protein, antibody formation, estrogen receptor, hormone related neoplasm /cancer, human therapy evaluation, interferon, monoclonal antibody, neoplasm /cancer hormone therapy, neoplasm /cancer immunodiagnosis, neoplastic cell, postmenopause, progesterone receptor, surface antigen body fluid, female, histochemistry /cytochemistry, histopathology, immunofluorescence technique, laboratory rabbit, tissue /cell culture
    IMMUNOHISTOCHEMICAL CLASSIFICATION OF HUMAN BREAST TUMOR
    (1991)

    Abstract :

    This proposal addresses the important issue of hormone therapy failures among post-menopausal women with estrogen receptor- positive ER(+) breast cancer with or without progesterone receptors (PR). Clinical correlation studies have shown that the current methods of sub-classification of ER(+) tumors based on the presence/absence of proteins which are markers of estrogen action (ex. PR) are inadequate for precise differentiation of truly hormone-responsive from hormone-resistant ER(+) tumors. The level of prediction error (30% ER+/PR+ failures and 25-30% ER+/PR- responders to hormone therapy) translates to significant proportions because 75% of 100,000 newly diagnosed cases of breast cancer will be ER(+) and 50-60% of these will be PR(+). A precise sub-classification of primary biopsies of ER(+) tumors will be valuable for early selection of potential hormone therapy failures when the tumor burden is small so that alternative therapies can be administered to benefit the patient. With the help of polyclonal antibodies (Pab) to ER, in-vitro hormone incubation procedure and immunohistochemistry (IF) developed in our lab we have identified two varieties of ER in human cancers which, although capable of binding estrogens with high affinity, are defective in their nuclear binding function. Preliminary clinical correlation data have also revealed a preponderance of these defective ER among those breast cancers which are hormone resistant and of non-defective ER among those which are responsive to hormone therapy. Based on these results and of previous investigations emphasizing a correlation between defective ER and hormone- independent growth WE PROPOSE THAT A SUB-CLASSIFICATION OF ER(+) TUMORS BASED ON NUCLEAR BINDING CHARACTERISTICS MAY DISCERN TRULY HORMONE-DEPENDENT TUMORS FROM RESISTANT ONES. Our SPECIFIC GOALS , therefore, are: (1) To develop novel monoclonal antibodies (Mabs) to identify and discriminate among the defective/non-defective ER based on their epitope differences; (2) To immunotype with Pabs and IF, the ER in established ER(+) human breast cancer cell lines with known hormone response data; (3) To attempt establishment of primary cultures from malignant fluids of patients with ER(+) tumors who failed hormone therapy and to immunotype ER with Pabs; (4) To immunotype sequential biopsies of ER(+) tumors (primary vs recurrent) to find out if recurrences become enriched in cells with defective ER; to increase patient population for clinical response to hormone therapy.


    Project Number : 2R01CA037944-04A1
    ICD : NATIONAL CANCER INSTITUTE
    IRG : EI
    Project Terms : NEOPLASMS CLASSIFICATION AND STAGING, NEOPLASMS DIAGNOSIS, BREAST NEOPLASMS DIAGNOSIS, NEOPLASMS OF REPRODUCTIVE SYSTEM, BREAST NEOPLASMS FERTILITY-INFERTILITY, SEX CYCLES, POSTMENOPAUSE, IMMUNITY, CYTOKINES, LYMPHOKINES, INTERFERONS, IMMUNOLOGICAL PREPARATIONS, MONOCLONAL ANTIBODIES, IMMUNOLOGY, ANTIBODY FORMATION, IMMUNOLOGY, ANTIGENS, SURFACE ANTIGENS, NEOPLASMS DIAGNOSIS, IMMUNODIAGNOSIS OF NEOPLASMS, NEOPLASMS, HORMONE INDUCED OR DEPENDENT, NEOPLASTIC CELLS, NEOPLASTIC THERAPY, CANCER CHEMOTHERAPY, HORMONE THERAPY, PROTEINS, BINDING PROTEINS, DNA-BINDING PROTEINS, RECEPTORS, HORMONE RECEPTORS, STEROID HORMONE RECEPTORS, ESTROGEN RECEPTORS, RECEPTORS, HORMONE RECEPTORS, STEROID HORMONE RECEPTORS, PROGESTERONE RECEPTORS, THERAPY EVALUATION, HUMAN ANIMALS, CHORDATES, MAMMALS, LAGOMORPHS, BODY FLUIDS (AND RELATED SUBSTANCES), HISTOCHEMISTRY AND CYTOCHEMISTRY, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, SEX, FEMALE, TISSUE (CELL) CULTURE, histopathology
    IMMUNOHISTOCHEMICAL CLASSIFICATION OF HUMAN BREAST TUMOR
    (1991)

    Abstract :

    This proposal addresses the important issue of hormone therapy failures among post-menopausal women with estrogen receptor- positive ER(+) breast cancer with or without progesterone receptors (PR). Clinical correlation studies have shown that the current methods of sub-classification of ER(+) tumors based on the presence/absence of proteins which are markers of estrogen action (ex. PR) are inadequate for precise differentiation of truly hormone-responsive from hormone-resistant ER(+) tumors. The level of prediction error (30% ER+/PR+ failures and 25-30% ER+/PR- responders to hormone therapy) translates to significant proportions because 75% of 100,000 newly diagnosed cases of breast cancer will be ER(+) and 50-60% of these will be PR(+). A precise sub-classification of primary biopsies of ER(+) tumors will be valuable for early selection of potential hormone therapy failures when the tumor burden is small so that alternative therapies can be administered to benefit the patient. With the help of polyclonal antibodies (Pab) to ER, in-vitro hormone incubation procedure and immunohistochemistry (IF) developed in our lab we have identified two varieties of ER in human cancers which, although capable of binding estrogens with high affinity, are defective in their nuclear binding function. Preliminary clinical correlation data have also revealed a preponderance of these defective ER among those breast cancers which are hormone resistant and of non-defective ER among those which are responsive to hormone therapy. Based on these results and of previous investigations emphasizing a correlation between defective ER and hormone- independent growth WE PROPOSE THAT A SUB-CLASSIFICATION OF ER(+) TUMORS BASED ON NUCLEAR BINDING CHARACTERISTICS MAY DISCERN TRULY HORMONE-DEPENDENT TUMORS FROM RESISTANT ONES. Our SPECIFIC GOALS , therefore, are: (1) To develop novel monoclonal antibodies (Mabs) to identify and discriminate among the defective/non-defective ER based on their epitope differences; (2) To immunotype with Pabs and IF, the ER in established ER(+) human breast cancer cell lines with known hormone response data; (3) To attempt establishment of primary cultures from malignant fluids of patients with ER(+) tumors who failed hormone therapy and to immunotype ER with Pabs; (4) To immunotype sequential biopsies of ER(+) tumors (primary vs recurrent) to find out if recurrences become enriched in cells with defective ER; to increase patient population for clinical response to hormone therapy.


    Project Number : 5R01CA037944-05
    ICD : NATIONAL CANCER INSTITUTE
    IRG : EI
    Project Terms : NEOPLASMS CLASSIFICATION AND STAGING, NEOPLASMS DIAGNOSIS, BREAST NEOPLASMS DIAGNOSIS, NEOPLASMS OF REPRODUCTIVE SYSTEM, BREAST NEOPLASMS FERTILITY-INFERTILITY, SEX CYCLES, POSTMENOPAUSE, IMMUNITY, CYTOKINES, LYMPHOKINES, INTERFERONS, IMMUNOLOGICAL PREPARATIONS, MONOCLONAL ANTIBODIES, IMMUNOLOGY, ANTIBODY FORMATION, IMMUNOLOGY, ANTIGENS, SURFACE ANTIGENS, NEOPLASMS DIAGNOSIS, IMMUNODIAGNOSIS OF NEOPLASMS, NEOPLASMS, HORMONE INDUCED OR DEPENDENT, NEOPLASTIC CELLS, NEOPLASTIC THERAPY, CANCER CHEMOTHERAPY, HORMONE THERAPY, PROTEINS, BINDING PROTEINS, DNA-BINDING PROTEINS, RECEPTORS, HORMONE RECEPTORS, STEROID HORMONE RECEPTORS, ESTROGEN RECEPTORS, RECEPTORS, HORMONE RECEPTORS, STEROID HORMONE RECEPTORS, PROGESTERONE RECEPTORS, THERAPY EVALUATION, HUMAN ANIMALS, CHORDATES, MAMMALS, LAGOMORPHS, RABBITS (LABORATORY), BODY FLUIDS (AND RELATED SUBSTANCES), HISTOCHEMISTRY AND CYTOCHEMISTRY, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, SEX, FEMALE, TISSUE (CELL) CULTURE, histopathology
    IMMUNOHISTOCHEMISTRY OF HUMAN BREAST TUMORS: RABBIT POLYCLONAL ANTIBODIES
    (1989)
    Project Number : 2S07RR005382-280685
    ICD : NATIONAL CENTER FOR RESEARCH RESOURCES
    IMMUNOHISTOCHEMICAL CLASSIFICATION OF BREAST TUMORS
    (1988)

    Abstract :

    The rationale for the selection of hormonal versus chemotherapy for breast cancer patients is based on the biochemical parameter for hormone dependency, namely the presence of cytoplasmic estrogen receptors (ER). Tumors lacking ER and classified as hormone-independent rarely regress in response to hormonal therapies (additive or ablative). The frequency of "false negatives" in this group is only 10%. On the other hand, the probability of misclassification of ER-positive tumors as hormone-dependent and, therefore, as responders to hormone therapy is 40% if the presence of ER alone is considered relevant and 30% if the presence of ER and another hormone receptor, progesterone receptor (PR), is taken into account. Since ER-positive tumors are the more predominant kind (75% of all breast cancers are ER positive) there is a need for greater accuracy in the selection of truly hormone-dependent tumors for hormonal therapy. In addition, cytoplasmic ER is also a marker protein for better prognosis, late recurrence pattern, and longer disease-free survival. We propose to examine the utility of classification of breast tumors based on immunohistochemical parameters either applied individually or in conjunction with the biochemical data on ER for more precise selection of hormone-dependent from hormone-indifferent tumors. Two different approaches to immunohistochemical classification will be compared for their relative merits: (1)\classification based on the proportion of ER-positive and ER-negative tumor cell population. This will be achieved by analyzing frozen sections from multiple areas of the tumor for the density of ER-positive and ER-negative cells. ER-positive cells will be identified by immunofluorescent (IF) procedure using polyclonal antibodies specific for Type I ER; and (2)\transportation of E2 via transformed ER to specific nuclear acceptor sites is a prerequisite for all the molecular events (including PR synthesis) that are dependent on estrogen. Using immunohistochemical procedures ER-positive tumors will be sub-classified on the basis of the density of ER-positive cells that can translocate their ER, in vitro, when exposed to estrogenic or antiestrogenic ligands. An interesting and significant observation has been the following: Preliminary immunohistochemical studies on 60 ER + tumors (30 PR+, 30 PR(-)) have revealed that 80% of the PR (-) tumors have an abnormality which is expressed as an inability of in vitro translocation of ER-E2 to the nuclear acceptor sites. The efficacy of this mode of classification for selecting the hormone-dependent tumors will be compared with that of the biochemical mode of classification based on the presence/absence of PR for selecting the hormone responders in the ER-positive group. (2)


    Project Number : 5R01CA037944-03
    ICD : NATIONAL CANCER INSTITUTE
    IRG : PTHB
    Project Terms : ENDOCRINOLOGY, HORMONE RECEPTORS, ESTROGEN RECEPTORS, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, NEOPLASMS CLASSIFICATION AND STAGING, NEOPLASMS DIAGNOSIS, BREAST NEOPLASMS DIAGNOSIS, NEOPLASMS, HORMONE INDUCED OR DEPENDENT, PATHOLOGY B STUDY SECTION FERTILITY-INFERTILITY, SEX CYCLES, MENOPAUSE, IMMUNOLOGY, ANTIGENS, SURFACE ANTIGENS (GENERAL), NEOPLASMS DIAGNOSIS, IMMUNODIAGNOSIS OF NEOPLASMS, NEOPLASMS OF REPRODUCTIVE SYSTEM, BREAST NEOPLASMS, NEOPLASMS, CARCINOMA, NEOPLASTIC THERAPY, CANCER CHEMOTHERAPY, HORMONE THERAPY HISTOCHEMISTRY AND CYTOCHEMISTRY (GENERAL), HISTOPATHOLOGY (GENERAL), HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, RADIOTRACERS, TISSUE (CELL) CULTURE
    IMMUNOHISTOCHEMICAL CLASSIFICATION OF BREAST TUMORS
    (1988)

    Abstract :

    The rationale for the selection of hormonal versus chemotherapy for breast cancer patients is based on the biochemical parameter for hormone dependency, namely the presence of cytoplasmic estrogen receptors (ER). Tumors lacking ER and classified as hormone-independent rarely regress in response to hormonal therapies (additive or ablative). The frequency of "false negatives" in this group is only 10%. On the other hand, the probability of misclassification of ER-positive tumors as hormone-dependent and, therefore, as responders to hormone therapy is 40% if the presence of ER alone is considered relevant and 30% if the presence of ER and another hormone receptor, progesterone receptor (PR), is taken into account. Since ER-positive tumors are the more predominant kind (75% of all breast cancers are ER positive) there is a need for greater accuracy in the selection of truly hormone-dependent tumors for hormonal therapy. In addition, cytoplasmic ER is also a marker protein for better prognosis, late recurrence pattern, and longer disease-free survival. We propose to examine the utility of classification of breast tumors based on immunohistochemical parameters either applied individually or in conjunction with the biochemical data on ER for more precise selection of hormone-dependent from hormone-indifferent tumors. Two different approaches to immunohistochemical classification will be compared for their relative merits: (1)\classification based on the proportion of ER-positive and ER-negative tumor cell population. This will be achieved by analyzing frozen sections from multiple areas of the tumor for the density of ER-positive and ER-negative cells. ER-positive cells will be identified by immunofluorescent (IF) procedure using polyclonal antibodies specific for Type I ER; and (2)\transportation of E2 via transformed ER to specific nuclear acceptor sites is a prerequisite for all the molecular events (including PR synthesis) that are dependent on estrogen. Using immunohistochemical procedures ER-positive tumors will be sub-classified on the basis of the density of ER-positive cells that can translocate their ER, in vitro, when exposed to estrogenic or antiestrogenic ligands. An interesting and significant observation has been the following: Preliminary immunohistochemical studies on 60 ER + tumors (30 PR+, 30 PR(-)) have revealed that 80% of the PR (-) tumors have an abnormality which is expressed as an inability of in vitro translocation of ER-E2 to the nuclear acceptor sites. The efficacy of this mode of classification for selecting the hormone-dependent tumors will be compared with that of the biochemical mode of classification based on the presence/absence of PR for selecting the hormone responders in the ER-positive group. (2)


    Project Number : 3R01CA037944-03S1
    ICD : NATIONAL CANCER INSTITUTE
    IRG : PTHB
    Project Terms : ENDOCRINOLOGY, HORMONE RECEPTORS, ESTROGEN RECEPTORS, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, NEOPLASMS CLASSIFICATION AND STAGING, NEOPLASMS DIAGNOSIS, BREAST NEOPLASMS DIAGNOSIS, NEOPLASMS, HORMONE INDUCED OR DEPENDENT, PATHOLOGY B STUDY SECTION FERTILITY-INFERTILITY, SEX CYCLES, MENOPAUSE, IMMUNOLOGY, ANTIGENS, SURFACE ANTIGENS (GENERAL), NEOPLASMS DIAGNOSIS, IMMUNODIAGNOSIS OF NEOPLASMS, NEOPLASMS OF REPRODUCTIVE SYSTEM, BREAST NEOPLASMS, NEOPLASMS, CARCINOMA, NEOPLASTIC THERAPY, CANCER CHEMOTHERAPY, HORMONE THERAPY HISTOCHEMISTRY AND CYTOCHEMISTRY (GENERAL), HISTOPATHOLOGY (GENERAL), HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, RADIOTRACERS, TISSUE (CELL) CULTURE
    IMMUNOHISTOCHEMICAL CLASSIFICATION OF HUMAN BREAST TUMORS: POLYCLONAL ANTIBODIES
    (1988)
    Project Number : 2S07RR005382-270096
    ICD : NATIONAL CENTER FOR RESEARCH RESOURCES
    IMMUNOHISTOCHEMICAL CLASSIFICATION OF BREAST TUMORS
    (1987)

    Abstract :

    The rationale for the selection of hormonal versus chemotherapy for breast cancer patients is based on the biochemical parameter for hormone dependency, namely the presence of cytoplasmic estrogen receptors (ER). Tumors lacking ER and classified as hormone-independent rarely regress in response to hormonal therapies (additive or ablative). The frequency of "false negatives" in this group is only 10%. On the other hand, the probability of misclassification of ER-positive tumors is hormone-dependent and, therefore, as responders to hormone therapy is 40% if the presence of ER alone is considered relevant and 30% if the presence of ER and another hormone receptor, progesterone receptor (PR), is taken into account. Since ER-positive tumors are the more predominant kind (75% of all breast cancers are ER+) there is a need for greater accuracy in the selection of truly hormone-dependent tumors for hormonal therapy. In addition, cytoplasmic ER is also a marker protein for better prognosis, late recurrence pattern, and longer disease-free survival. We propose to examine the utility of classification of breast tumors based on immunohistochemical parameters either applied individually or in conjunction with the biochemical data on ER for more precise selection of hormone-dependent from hormone-indifferent tumors. Two different approaches to immunohistochemical classification will be compared for their relative merits: (a)\Classification based on the proportion of ER-positive and ER-negative tumor cell population. This will be achieved by analyzing frozen sections from multiple areas of the tumor for the density of ER-positive and ER-negative cells. ER-positive cells will be identified by immunofluorescent (IF) procedure using polyclonal antibodies specific for Type I ER; (b)\Transportation of E2via transformed ER to specific nuclear acceptor sites is a prerequisite for all the molecular events (including PR synthesis) that are dependent on estrogen. Using immunohistochemical procedures ER-positive tumors will be sub-classified on the basis of the density of ER-positive cells that can translocate their ER, in vitro, when exposed to estrogenic or antiestrogenic ligands. The efficacy of this mode of classification for selecting the hormone-dependent tumors will be compared with that of the biochemical mode of classification based on the presence/absence of PR for selecting the hormone responders in the ER-positive group. (2)


    Project Number : 1R01CA037944-01
    ICD : NATIONAL CANCER INSTITUTE
    IRG : PTHB
    Project Terms : ENDOCRINOLOGY, HORMONE RECEPTORS, ESTROGEN RECEPTORS, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, NEOPLASMS CLASSIFICATION AND STAGING, NEOPLASMS DIAGNOSIS, BREAST NEOPLASMS DIAGNOSIS, NEOPLASMS, HORMONE INDUCED OR DEPENDENT, PATHOLOGY B STUDY SECTION FERTILITY-INFERTILITY, SEX CYCLES, MENOPAUSE, IMMUNOLOGY, ANTIGENS, SURFACE ANTIGENS (GENERAL), NEOPLASMS DIAGNOSIS, IMMUNODIAGNOSIS OF NEOPLASMS, NEOPLASMS OF REPRODUCTIVE SYSTEM, BREAST NEOPLASMS, NEOPLASMS, CARCINOMA, NEOPLASTIC THERAPY, CANCER CHEMOTHERAPY, HORMONE THERAPY HISTOCHEMISTRY AND CYTOCHEMISTRY (GENERAL), HISTOPATHOLOGY (GENERAL), HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, RADIOTRACERS, TISSUE (CELL) CULTURE
    IMMUNOHISTOCHEMICAL CLASSIFICATION OF BREAST TUMORS
    (1987)

    Abstract :

    The rationale for the selection of hormonal versus chemotherapy for breast cancer patients is based on the biochemical parameter for hormone dependency, namely the presence of cytoplasmic estrogen receptors (ER). Tumors lacking ER and classified as hormone-independent rarely regress in response to hormonal therapies (additive or ablative). The frequency of "false negatives" in this group is only 10%. On the other hand, the probability of misclassification of ER-positive tumors as hormone-dependent and, therefore, as responders to hormone therapy is 40% if the presence of ER alone is considered relevant and 30% if the presence of ER and another hormone receptor, progesterone receptor (PR), is taken into account. Since ER-positive tumors are the more predominant kind (75% of all breast cancers are ER positive) there is a need for greater accuracy in the selection of truly hormone-dependent tumors for hormonal therapy. In addition, cytoplasmic ER is also a marker protein for better prognosis, late recurrence pattern, and longer disease-free survival. We propose to examine the utility of classification of breast tumors based on immunohistochemical parameters either applied individually or in conjunction with the biochemical data on ER for more precise selection of hormone-dependent from hormone-indifferent tumors. Two different approaches to immunohistochemical classification will be compared for their relative merits: (1)\classification based on the proportion of ER-positive and ER-negative tumor cell population. This will be achieved by analyzing frozen sections from multiple areas of the tumor for the density of ER-positive and ER-negative cells. ER-positive cells will be identified by immunofluorescent (IF) procedure using polyclonal antibodies specific for Type I ER; and (2)\transportation of E2 via transformed ER to specific nuclear acceptor sites is a prerequisite for all the molecular events (including PR synthesis) that are dependent on estrogen. Using immunohistochemical procedures ER-positive tumors will be sub-classified on the basis of the density of ER-positive cells that can translocate their ER, in vitro, when exposed to estrogenic or antiestrogenic ligands. An interesting and significant observation has been the following: Preliminary immunohistochemical studies on 60 ER + tumors (30 PR+, 30 PR(-)) have revealed that 80% of the PR (-) tumors have an abnormality which is expressed as an inability of in vitro translocation of ER-E2 to the nuclear acceptor sites. The efficacy of this mode of classification for selecting the hormone-dependent tumors will be compared with that of the biochemical mode of classification based on the presence/absence of PR for selecting the hormone responders in the ER-positive group. (2)


    Project Number : 5R01CA037944-02
    ICD : NATIONAL CANCER INSTITUTE
    IRG : PTHB
    Project Terms : ENDOCRINOLOGY, HORMONE RECEPTORS, ESTROGEN RECEPTORS, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, NEOPLASMS CLASSIFICATION AND STAGING, NEOPLASMS DIAGNOSIS, BREAST NEOPLASMS DIAGNOSIS, NEOPLASMS, HORMONE INDUCED OR DEPENDENT, PATHOLOGY B STUDY SECTION FERTILITY-INFERTILITY, SEX CYCLES, MENOPAUSE, IMMUNOLOGY, ANTIGENS, SURFACE ANTIGENS (GENERAL), NEOPLASMS DIAGNOSIS, IMMUNODIAGNOSIS OF NEOPLASMS, NEOPLASMS OF REPRODUCTIVE SYSTEM, BREAST NEOPLASMS, NEOPLASMS, CARCINOMA, NEOPLASTIC THERAPY, CANCER CHEMOTHERAPY, HORMONE THERAPY HISTOCHEMISTRY AND CYTOCHEMISTRY (GENERAL), HISTOPATHOLOGY (GENERAL), HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, RADIOTRACERS, TISSUE (CELL) CULTURE


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