Hadi Yaziji - Academia.edu (original) (raw)

Papers by Hadi Yaziji

The American Journal of Surgical Pathology, Sep 1, 1996

ABSTRACT

Advances in Anatomic Pathology, Mar 1, 2000

Pathology Case Reviews, Nov 1, 1999

International Journal of Surgical Pathology, 2003

While historically detection of premelanosomes by electron microscopic studies was the only means... more While historically detection of premelanosomes by electron microscopic studies was the only means possible of confirming melanocytic lineage of a neoplastic process, advances in the field of immunohistochemistry have allowed for accurate and reliable diagnosis using antibodies to 1 of a number of melanocyte-restricted proteins. S-100 was the first such marker exploited by immunohistochemistry; subsequently, the HMB45 monoclonal antibody to gplOO became widely used as a sensitive and specific melanocytic marker. More recently, antibodies to other melanocytic proteins have become available, inciuding the MART-1 gene product and microphthalmia transcription factor. This article provides a brief overview of these markers in terms of their specificity and sensitivity and offers a discussion of tumors with partial melanocytic differentiation.

American Journal of Clinical Pathology, Jun 1, 2001

We correlated quantitative results obtained in 40 invasive breast cancer cases for HER-2 gene amp... more We correlated quantitative results obtained in 40 invasive breast cancer cases for HER-2 gene amplification by fluorescence in situ hybridization with protein expression by immunohistochemical studies with computer-assisted image analysis. Fluorescence in situ hybridization (FISH) results were quantified as the mean number of fluorescent signals per nucleus, and immunohistochemical slides were read by semiquantitatively assessing membranous immunostaining intensity in tumor cells vs nonneoplastic breast tissue or quantitatively evaluated by image analysis. We found high correlation between immunohistochemical results by semiquantitative scoring and by image analysis. FISH results correlated with immunohistochemical results moderately when the staining intensity of only tumor cells was assessed and significantly better when the difference in staining intensity between tumor cells and nonneoplastic breast tissue was assessed. The correlation with FISH results was further improved when immunohistochemical study was combined with heat-induced epitope retrieval (HIER). Although FISH and immunohistochemical studies assess different aspects of the HER-2/neu gene (amplification vs overexpression), we found good correlation between the diagnostic techniques. The correlation was best when immunohistochemical studies were combined with HIER and assessed as the difference between tumor cells and nonneoplastic breast tissue.

Applied Immunohistochemistry & Molecular Morphology, Jun 1, 2004

ABSTRACT

Modern Pathology, 2006

We evaluated the sensitivity and specificity of 10 monoclonal and two polyclonal antibodies for d... more We evaluated the sensitivity and specificity of 10 monoclonal and two polyclonal antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma (AdCA) using immunohistochemistry (IHC). The antibodies were directed against the mesothelial-associated antigens mesothelin, calretinin, cytokeratin 5, thrombomodulin, Wilms' tumor-1 (WT-1) gene product and HBME-1, and the nonmesothelial antigens Lewis-Y blood group (antibody BG8), MOC-31, BerEp4, CD15, and carcinoembryonic antigen (CEA) family. The 133 tumors evaluated included 65 malignant epithelioid mesotheliomas, 22 lung AdCAs, 27 ovarian serous carcinomas, 24 breast carcinomas, and five gastric carcinomas. Diagnoses were based on clinical, histologic, ultrastructural, and/or IHC findings. Calretinin had the best sensitivity for mesothelioma (95%), followed by HBME-1 (84%), WT-1 (78%), cytokeratin 5 (76%), mesothelin (75%), and vimentin and thrombomodulin (68%). Thrombomodulin had the best specificity for mesothelioma (92%), followed by cytokeratin 5 (89%), calretinin (87%) vimentin (84%), and HBME-1 (45%). When ovarian carcinomas were excluded from the analysis, the specificity of mesothelin and WT-1 for the diagnosis of mesothelioma increased to 90 and 81%, respectively. The sensitivity of the nonmesothelial antigens for AdCA was organ dependent, with BG8 performing best in the breast cancer group (96%), and BerEp4, BG8, MOC-31 performing best in the lung cancer group (100%). The specificity of the nonmesothelial antigens for AdCA was 98% for BG8 and CEA, 97% for CD15, 95% for BerEp4, and 87% for MOC-31. A novel statistical analysis technique employing logic regression analysis identified a three-antibody immunohistochemical panel including calretinin, BG8, and MOC-31, which provided over 96% sensitivity and specificity for distinguishing epithelioid mesothelioma from AdCA.

American Journal of Clinical Pathology, Apr 1, 2001

The American Journal of Surgical Pathology, Dec 1, 2002

Modern Pathology, Jul 1, 2000

To the Editor: We read with interest the study by Varma et al. (1) on the effects of fixation and... more To the Editor: We read with interest the study by Varma et al. (1) on the effects of fixation and tissue pretreatment (i.e., use of heat-induced epitope retrieval [HIER] techniques) on the reliability of the use of antibody clone 34␤E12, directed against high-molecular-weight cytokeratins (HMWCK), to identify the outer cell layer in prostate epithelium. However, the accompanying editorial by Ramnani and Bostwick (2) seems to represent an attempt to derive a conclusion neither suggested nor demonstrated by the cited study of Varma et al. Ramnani and Bostwick concluded that laboratories should "exercise caution" in the application and interpretation of results using 34␤E12 in distinguishing benign from malignant prostate glands. The study of Varma et al., however, is purely a technical one and did not address the issue of sensitivity and specificity of the finding of loss of HMWCK-positive cells in prostate tissue. It is important, in our judgment, to separate the technical from clinical questions, although we disagree with Drs. Ramnani and Bostwick on both counts. Ramnani and Bostwick noted in their editorial that "we and others have noted that this antibody is temperamental and prone to variability in staining," but Drs. Ramnani and Bostwick did not mention whether this "temperamental" performance incorporates the HIER pretreatment scheme suggested by Varma et al.; certainly the data presented by Varma et al. contradict this statement. We could list scores of clinically useful antibodies, the performance of which could be characterized as "temperamental and prone to variability in staining" if inappropriate or inadequate HIER techniques are performed before their use. Antibodies to chromogranin A, for example, without adequate HIER, can be an unreliable marker of neuroendocrine carcinomas, but with appropriate HIER, their sensitivity for these tumors is well in excess of 90%. Thus, antibody 34␤E12 is no different from other antibodies in this regard, and Varma et al. have provided us with useful technical guidelines to optimize antibody use. Furthermore, Varma et al. offered reassuring evidence that although prolonged formalin fixation can result in a progressive decrease in the immunostaining intensity with antibody 34␤E12, this becomes a significant problem only after for

Histochemical Journal, Mar 1, 1996

Tartrate-resistant acid phosphatase is an inducible marker of cell differentiation and activation... more Tartrate-resistant acid phosphatase is an inducible marker of cell differentiation and activation expressed by specialized cells of macrophage lineage and some activated lymphocytes. Clinically, this phosphatase is a diagnostic marker for hairy cell leukaemia and osteoclast activity. The cDNA for this enzyme has been cloned from a placental expression library, yet the cell(s) expressing the enzyme protein has not been determined with certainty. Our laboratories have developed a monoclonal antibody, 9C5, suitable for immunohistochemical localization of tartrate-resistant acid phosphatase in paraffin sections. The purpose of this study was to use antibody 9C5 to identify cells expressing tartrate-resistant acid phosphatase in sections of paraffin-embedded, normal, full-term placenta and to determine if those cells expressed other macrophage markers including CD68 (PG-M1 antibody), LN5, lysozyme, alpha 1-antitrypsin and alpha 1-antichymotrypsin. Histochemical localization of activity in frozen sections was compared with immunohistochemical localization in paraffin sections of the same tissue specimens. The activity and antigenicity of this enzyme were detected in decidual cells, syncytiotrophoblast, and some macrophages distributed throughout maternal and embryonic tissues, but not in neutrophils. Unlike other tissues previously examined, placenta contains significant numbers of the phosphate-positive cells that are not of macrophage origin.

Archives of Pathology & Laboratory Medicine, Jun 1, 2001

Background.-Renal angiomyolipoma is a benign tumor histologically characterized by proliferation ... more Background.-Renal angiomyolipoma is a benign tumor histologically characterized by proliferation of spindle cells, epithelioid cells, and adipocytic cells in concert with many thick-walled blood vessels. To add further diagnostic confusion, an epithelioid cell-predominant variant of renal angiomyolipoma has recently been described. HMB-45 immunoreactivity correlates with ultrastructural striated organelles that closely resemble premelanosomes, although no evidence of melanogenesis has been documented in this tumor. Objective.-To further characterize the immunophenotypic and ultrastructural profile of renal angiomyolipoma based on phenotypic cell type (epithelioid, spindle, and adipocytic cell). Design.-Formalin-fixed, paraffin-embedded tissues from 27 renal angiomyolipomas and 8 renal cell carcinomas were immunostained with monoclonal antibodies to the melanoma-associated antigens HMB-45, HMB-50, NKI/C3 (CD63), and tyrosinase; the smooth muscle-related antigens calponin and muscle-specific actin (HHF-35); S100; and cytokeratin (CK). All renal angiomyolipomas were also immunostained with a polyclonal antibody to renin. Ultrastructural examination was performed on 9 selected cases. Results.-All renal angiomyolipomas stained positive for HMB-45, HMB-50, NKI/C3, muscle-specific actin (HHF-35), and calponin. Overall, HMB-45, HMB-50, and NKI/ C3 preferentially stained the epithelioid cells. Tyrosinase staining was present in 50% of the renal angiomyolipomas with adequate tissue for staining (12 of 24 cases); positive staining and intensity paralleled HMB-45, HMB-50, and NKI/C3. Muscle-specific actin (HHF-35) and calponin preferentially stained the spindle cells. The adipocytic cells stained positive for both melanoma-associated antigens and smooth muscle antigens. Epithelioid cells, spindle cells, and adipocytic cells were CK, S100, and renin negative. Ultrastructural findings paralleled immunohistochemical staining patterns. Premelanosome-like organelles and electron dense granules were more readily detected in the epithelioid cells within the tumor, whereas ultrastructural characteristics of smooth muscle cells were more easily found in the spindle cells. All renal cell carcinomas stained positive for CK, NKI/C3 staining was variable, and all were negative for HMB-45, HMB-50, smooth muscle actin (HHF-35), and calponin. Conclusion.-In renal angiomyolipoma, the epithelioid and spindle cells have preferential staining patterns for melanoma-associated antigens versus smooth muscle antigens, respectively. Positivity in renal angiomyolipoma for HMB-50, NKI/C3, and tyrosinase, in addition to HMB-45, provides evidence for the presence of different melanomaassociated gene products. Immunophenotypic overlap of the 3 histologically distinct renal angiomyolipoma cell populations suggests a common cell line, supporting a unitarian concept for renal angiomyolipoma. Ultrastructural characteristics of the 3 renal angiomyolipoma cell phenotypes parallel the immunophenotype, giving further support to a common cell line. Our study lends further credence to the perivascular epithelioid cell concept as proposed by Bonetti and colleagues.

American Journal of Clinical Pathology, Feb 1, 2000

Applied Immunohistochemistry & Molecular Morphology, Dec 1, 2008

Estrogen receptor (ER) status in breast cancer is currently the most important predictive biomark... more Estrogen receptor (ER) status in breast cancer is currently the most important predictive biomarker that determines breast cancer prognosis after treatment with endocrine therapy. Although immunohistochemistry has been widely viewed as the gold standard methodology for ER testing in breast cancer, lack of standardized procedures, and lack of regulatory adherence to testing guidelines has resulted in high rates of "false-negative" results worldwide. Standardized testing is only possible after all aspects of ER testing--preanalytical, analytical, and postanalytical, have been closely controlled. A meeting of the "ad-hoc committee" of expert pathologists, technologists, and scientists, representing academic centers, reference laboratories, and various agencies, issued standardization testing recommendations, aimed at optimization of clinical ER testing environment, as a step toward improved standardized testing.

The American Journal of Surgical Pathology, Aug 1, 2001

Low-grade fibromatosis-like spindle cell carcinoma is a

The American Journal of Surgical Pathology, Sep 1, 1996

ABSTRACT

Advances in Anatomic Pathology, Mar 1, 2000

Pathology Case Reviews, Nov 1, 1999

International Journal of Surgical Pathology, 2003

While historically detection of premelanosomes by electron microscopic studies was the only means... more While historically detection of premelanosomes by electron microscopic studies was the only means possible of confirming melanocytic lineage of a neoplastic process, advances in the field of immunohistochemistry have allowed for accurate and reliable diagnosis using antibodies to 1 of a number of melanocyte-restricted proteins. S-100 was the first such marker exploited by immunohistochemistry; subsequently, the HMB45 monoclonal antibody to gplOO became widely used as a sensitive and specific melanocytic marker. More recently, antibodies to other melanocytic proteins have become available, inciuding the MART-1 gene product and microphthalmia transcription factor. This article provides a brief overview of these markers in terms of their specificity and sensitivity and offers a discussion of tumors with partial melanocytic differentiation.

American Journal of Clinical Pathology, Jun 1, 2001

We correlated quantitative results obtained in 40 invasive breast cancer cases for HER-2 gene amp... more We correlated quantitative results obtained in 40 invasive breast cancer cases for HER-2 gene amplification by fluorescence in situ hybridization with protein expression by immunohistochemical studies with computer-assisted image analysis. Fluorescence in situ hybridization (FISH) results were quantified as the mean number of fluorescent signals per nucleus, and immunohistochemical slides were read by semiquantitatively assessing membranous immunostaining intensity in tumor cells vs nonneoplastic breast tissue or quantitatively evaluated by image analysis. We found high correlation between immunohistochemical results by semiquantitative scoring and by image analysis. FISH results correlated with immunohistochemical results moderately when the staining intensity of only tumor cells was assessed and significantly better when the difference in staining intensity between tumor cells and nonneoplastic breast tissue was assessed. The correlation with FISH results was further improved when immunohistochemical study was combined with heat-induced epitope retrieval (HIER). Although FISH and immunohistochemical studies assess different aspects of the HER-2/neu gene (amplification vs overexpression), we found good correlation between the diagnostic techniques. The correlation was best when immunohistochemical studies were combined with HIER and assessed as the difference between tumor cells and nonneoplastic breast tissue.

Applied Immunohistochemistry & Molecular Morphology, Jun 1, 2004

ABSTRACT

Modern Pathology, 2006

We evaluated the sensitivity and specificity of 10 monoclonal and two polyclonal antibodies for d... more We evaluated the sensitivity and specificity of 10 monoclonal and two polyclonal antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma (AdCA) using immunohistochemistry (IHC). The antibodies were directed against the mesothelial-associated antigens mesothelin, calretinin, cytokeratin 5, thrombomodulin, Wilms' tumor-1 (WT-1) gene product and HBME-1, and the nonmesothelial antigens Lewis-Y blood group (antibody BG8), MOC-31, BerEp4, CD15, and carcinoembryonic antigen (CEA) family. The 133 tumors evaluated included 65 malignant epithelioid mesotheliomas, 22 lung AdCAs, 27 ovarian serous carcinomas, 24 breast carcinomas, and five gastric carcinomas. Diagnoses were based on clinical, histologic, ultrastructural, and/or IHC findings. Calretinin had the best sensitivity for mesothelioma (95%), followed by HBME-1 (84%), WT-1 (78%), cytokeratin 5 (76%), mesothelin (75%), and vimentin and thrombomodulin (68%). Thrombomodulin had the best specificity for mesothelioma (92%), followed by cytokeratin 5 (89%), calretinin (87%) vimentin (84%), and HBME-1 (45%). When ovarian carcinomas were excluded from the analysis, the specificity of mesothelin and WT-1 for the diagnosis of mesothelioma increased to 90 and 81%, respectively. The sensitivity of the nonmesothelial antigens for AdCA was organ dependent, with BG8 performing best in the breast cancer group (96%), and BerEp4, BG8, MOC-31 performing best in the lung cancer group (100%). The specificity of the nonmesothelial antigens for AdCA was 98% for BG8 and CEA, 97% for CD15, 95% for BerEp4, and 87% for MOC-31. A novel statistical analysis technique employing logic regression analysis identified a three-antibody immunohistochemical panel including calretinin, BG8, and MOC-31, which provided over 96% sensitivity and specificity for distinguishing epithelioid mesothelioma from AdCA.

American Journal of Clinical Pathology, Apr 1, 2001

The American Journal of Surgical Pathology, Dec 1, 2002

Modern Pathology, Jul 1, 2000

To the Editor: We read with interest the study by Varma et al. (1) on the effects of fixation and... more To the Editor: We read with interest the study by Varma et al. (1) on the effects of fixation and tissue pretreatment (i.e., use of heat-induced epitope retrieval [HIER] techniques) on the reliability of the use of antibody clone 34␤E12, directed against high-molecular-weight cytokeratins (HMWCK), to identify the outer cell layer in prostate epithelium. However, the accompanying editorial by Ramnani and Bostwick (2) seems to represent an attempt to derive a conclusion neither suggested nor demonstrated by the cited study of Varma et al. Ramnani and Bostwick concluded that laboratories should "exercise caution" in the application and interpretation of results using 34␤E12 in distinguishing benign from malignant prostate glands. The study of Varma et al., however, is purely a technical one and did not address the issue of sensitivity and specificity of the finding of loss of HMWCK-positive cells in prostate tissue. It is important, in our judgment, to separate the technical from clinical questions, although we disagree with Drs. Ramnani and Bostwick on both counts. Ramnani and Bostwick noted in their editorial that "we and others have noted that this antibody is temperamental and prone to variability in staining," but Drs. Ramnani and Bostwick did not mention whether this "temperamental" performance incorporates the HIER pretreatment scheme suggested by Varma et al.; certainly the data presented by Varma et al. contradict this statement. We could list scores of clinically useful antibodies, the performance of which could be characterized as "temperamental and prone to variability in staining" if inappropriate or inadequate HIER techniques are performed before their use. Antibodies to chromogranin A, for example, without adequate HIER, can be an unreliable marker of neuroendocrine carcinomas, but with appropriate HIER, their sensitivity for these tumors is well in excess of 90%. Thus, antibody 34␤E12 is no different from other antibodies in this regard, and Varma et al. have provided us with useful technical guidelines to optimize antibody use. Furthermore, Varma et al. offered reassuring evidence that although prolonged formalin fixation can result in a progressive decrease in the immunostaining intensity with antibody 34␤E12, this becomes a significant problem only after for

Histochemical Journal, Mar 1, 1996

Tartrate-resistant acid phosphatase is an inducible marker of cell differentiation and activation... more Tartrate-resistant acid phosphatase is an inducible marker of cell differentiation and activation expressed by specialized cells of macrophage lineage and some activated lymphocytes. Clinically, this phosphatase is a diagnostic marker for hairy cell leukaemia and osteoclast activity. The cDNA for this enzyme has been cloned from a placental expression library, yet the cell(s) expressing the enzyme protein has not been determined with certainty. Our laboratories have developed a monoclonal antibody, 9C5, suitable for immunohistochemical localization of tartrate-resistant acid phosphatase in paraffin sections. The purpose of this study was to use antibody 9C5 to identify cells expressing tartrate-resistant acid phosphatase in sections of paraffin-embedded, normal, full-term placenta and to determine if those cells expressed other macrophage markers including CD68 (PG-M1 antibody), LN5, lysozyme, alpha 1-antitrypsin and alpha 1-antichymotrypsin. Histochemical localization of activity in frozen sections was compared with immunohistochemical localization in paraffin sections of the same tissue specimens. The activity and antigenicity of this enzyme were detected in decidual cells, syncytiotrophoblast, and some macrophages distributed throughout maternal and embryonic tissues, but not in neutrophils. Unlike other tissues previously examined, placenta contains significant numbers of the phosphate-positive cells that are not of macrophage origin.

Archives of Pathology & Laboratory Medicine, Jun 1, 2001

Background.-Renal angiomyolipoma is a benign tumor histologically characterized by proliferation ... more Background.-Renal angiomyolipoma is a benign tumor histologically characterized by proliferation of spindle cells, epithelioid cells, and adipocytic cells in concert with many thick-walled blood vessels. To add further diagnostic confusion, an epithelioid cell-predominant variant of renal angiomyolipoma has recently been described. HMB-45 immunoreactivity correlates with ultrastructural striated organelles that closely resemble premelanosomes, although no evidence of melanogenesis has been documented in this tumor. Objective.-To further characterize the immunophenotypic and ultrastructural profile of renal angiomyolipoma based on phenotypic cell type (epithelioid, spindle, and adipocytic cell). Design.-Formalin-fixed, paraffin-embedded tissues from 27 renal angiomyolipomas and 8 renal cell carcinomas were immunostained with monoclonal antibodies to the melanoma-associated antigens HMB-45, HMB-50, NKI/C3 (CD63), and tyrosinase; the smooth muscle-related antigens calponin and muscle-specific actin (HHF-35); S100; and cytokeratin (CK). All renal angiomyolipomas were also immunostained with a polyclonal antibody to renin. Ultrastructural examination was performed on 9 selected cases. Results.-All renal angiomyolipomas stained positive for HMB-45, HMB-50, NKI/C3, muscle-specific actin (HHF-35), and calponin. Overall, HMB-45, HMB-50, and NKI/ C3 preferentially stained the epithelioid cells. Tyrosinase staining was present in 50% of the renal angiomyolipomas with adequate tissue for staining (12 of 24 cases); positive staining and intensity paralleled HMB-45, HMB-50, and NKI/C3. Muscle-specific actin (HHF-35) and calponin preferentially stained the spindle cells. The adipocytic cells stained positive for both melanoma-associated antigens and smooth muscle antigens. Epithelioid cells, spindle cells, and adipocytic cells were CK, S100, and renin negative. Ultrastructural findings paralleled immunohistochemical staining patterns. Premelanosome-like organelles and electron dense granules were more readily detected in the epithelioid cells within the tumor, whereas ultrastructural characteristics of smooth muscle cells were more easily found in the spindle cells. All renal cell carcinomas stained positive for CK, NKI/C3 staining was variable, and all were negative for HMB-45, HMB-50, smooth muscle actin (HHF-35), and calponin. Conclusion.-In renal angiomyolipoma, the epithelioid and spindle cells have preferential staining patterns for melanoma-associated antigens versus smooth muscle antigens, respectively. Positivity in renal angiomyolipoma for HMB-50, NKI/C3, and tyrosinase, in addition to HMB-45, provides evidence for the presence of different melanomaassociated gene products. Immunophenotypic overlap of the 3 histologically distinct renal angiomyolipoma cell populations suggests a common cell line, supporting a unitarian concept for renal angiomyolipoma. Ultrastructural characteristics of the 3 renal angiomyolipoma cell phenotypes parallel the immunophenotype, giving further support to a common cell line. Our study lends further credence to the perivascular epithelioid cell concept as proposed by Bonetti and colleagues.

American Journal of Clinical Pathology, Feb 1, 2000

Applied Immunohistochemistry & Molecular Morphology, Dec 1, 2008

Estrogen receptor (ER) status in breast cancer is currently the most important predictive biomark... more Estrogen receptor (ER) status in breast cancer is currently the most important predictive biomarker that determines breast cancer prognosis after treatment with endocrine therapy. Although immunohistochemistry has been widely viewed as the gold standard methodology for ER testing in breast cancer, lack of standardized procedures, and lack of regulatory adherence to testing guidelines has resulted in high rates of "false-negative" results worldwide. Standardized testing is only possible after all aspects of ER testing--preanalytical, analytical, and postanalytical, have been closely controlled. A meeting of the "ad-hoc committee" of expert pathologists, technologists, and scientists, representing academic centers, reference laboratories, and various agencies, issued standardization testing recommendations, aimed at optimization of clinical ER testing environment, as a step toward improved standardized testing.

The American Journal of Surgical Pathology, Aug 1, 2001

Low-grade fibromatosis-like spindle cell carcinoma is a