Abstract – A review of histologic classification systems for grading of malignancy in squamous ce... more Abstract – A review of histologic classification systems for grading of malignancy in squamous cell carcinomas of the head and neck region is presented. Reasons behind the varying results obtained in studies using his tomorphologic grading schemes are presented and potential errors involved in this type of clinical research are discussed. Requirements for the study of correlations between malignancy grade scoring, and recurrence and survival rates are presented. These include factors as patient selection, clinical staging, and follow-up principles. Special attention must be given to treatment modalities, establishment of negative surgical margins and occurrence of regional lymph node and/or distant metastases.
A 7 year follow-up of 120 patients with malignant parotid cancers revealed parotidectomy to be an... more A 7 year follow-up of 120 patients with malignant parotid cancers revealed parotidectomy to be an adequate procedure for low-grade, nonaggressive lesions. The addition of radiation therapy postoperatively will improve local and regional control of high-grade, aggressive lesions. Postoperative radiation therapy may also make the removal of the facial nerve unnecessary in certain clinical presentations.
p73 and p63 are recently cloned genes that share considerable structural and functional homologie... more p73 and p63 are recently cloned genes that share considerable structural and functional homologies with the p53 tumor suppressor gene. These genes, unlike p53, express multiple mRNA isoforms with variable biologic functions, and their suppressor nature has yet to be confirmed. To determine the interrelationship between these genes in the tumorigenesis of head and neck squamous carcinoma (HNSC), we performed immunohistochemical analyses of their protein products and compared the data with clinicopathologic parameters in 38 patients. In histologically normal epithelium, p53 and p73 showed similar basal and/or parabasal expression, but that of p53 was weaker and discontinuous. p63 staining was noted in more suprabasal cellular layers and was stronger. In dysplasias, all three markers manifested variable but gradual increase in extent and intensity of cellular expression with histologic progression. In carcinomas, p63 was the most frequently expressed (94.7%), followed by p73 (68.4%) and p53 (52.6%). Significant statistical correlation was noted only between p63 and p73 expressions (P =.04). Although no statistical correlation was found between p53 and p63 or p73, p53-negative tumors overexpressed either p63 or p73. p73 expression was associated with distant metastasis and perineural/vascular invasion. Our study indicates that (1) p63 and p73 expression may represent an early event in HNSC tumorigenesis, (2) the lack of correlation between p73 or p63 and p53 expression suggests an independent and/or compensatory functional role, (3) p73 expression may play a part in HNSC progression, and (4) p73 and p63 may function as oncogenes in the development of these tumors. HUM PATHOL 33:158-164. Copyright 2002, Elsevier Science (USA). All rights reserved.
In a continually renewing cell population, stem cells can be regarded as a reservoir of cells wit... more In a continually renewing cell population, stem cells can be regarded as a reservoir of cells with a high capacity for self renewal that give rise to all differentiated progeny. They are the primary source for the generation and maintenance of cellular diversity and tissue homeostasis. In general, neoplasms manifest differentiation pathways similar to those found in the development and renewal of the normal tissues from which they arise. This feature serves as a basis for classification schemes of neoplasms and, as in the normal tissues, there is usually an inverse correlation between proliferative capacity and differentiation within the neoplasms. In our postulate of the histogenesis of salivary gland neoplasia, we evoke the stem cell model to account for the considerable phenotypic heterogeneity seen with these neoplasms. We further consider the neoplasms and, in particular, their myoepithelial constituencies to be manifestations of escape from normal regulatory mechanisms that determine differentiation pathways which a stem cell and its progeny can take. Clinical and basic scientific evidence are presented to support the postulate and also to point to the mitigating role that myoepithelial differentiation has in the biological course of salivary gland neoplasms.
... 2 Head and Neck Surgery, The University of Texas, MD Anderson Cancer Center, Houston. *Corres... more ... 2 Head and Neck Surgery, The University of Texas, MD Anderson Cancer Center, Houston. *Correspondence: Mario A. Luna MD, Department of Pathology, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Publication History. ...
A clinico-pathologic study of 12 patients, each harboring a hitherto not delineated adenocarcinom... more A clinico-pathologic study of 12 patients, each harboring a hitherto not delineated adenocarcinoma of salivary origin is presented. The authors have designated this histologically unique carcinoma as 'terminal duct adenocarcinoma' in deference not only to its light-optic appearance, but also to a putative origin from the reserve cells (epithelial and myoepithelial) of the intercalated duct. The tumors' local invasive properties with extension into nerves and adjacent bone suggest their biologic behavior is like that of adenoid cystic carcinomas.
Salivary duct carcinomas of the major salivary glands have two major distinguishing features. The... more Salivary duct carcinomas of the major salivary glands have two major distinguishing features. They closely resemble ductal carcinomas of the breast and they are high-grade malignancies. In general, but particularly for carcinomas measuring three or more centimeters in size, the clinical course is one characterized by a resistance to local control, metastases to regional lymph nodes and distant sites, and death within a few years after primary surgical treatment.
Abnormalities in chromosome 11q13 regions have been frequently found in head and neck squamous ca... more Abnormalities in chromosome 11q13 regions have been frequently found in head and neck squamous carcinoma. Recent studies indicate that the PRAD-1 (also CCND1), which encodes cyclin D1, is a putative oncogene that is an important component of this region. DNA was extracted from 32 snap-frozen specimens from primary head and neck squamous carcinomas. DNA from peripheral blood lymphocytes, normal mucosa, and salivary gland tissue were used as controls. A genomic DNA probe containing the first exon of PRAD-1 was used for hybridization with specimen DNAs by the Southern technique. A 5.6-kb genomic DNA probe of immunoglobulin heavy chain was used as an internal standard for assessing PRAD-1 amplification. Eleven (34.4%) squamous carcinoma specimens showed PRAD-1 amplification (2- to 10-fold). Although no significant statistical correlation among amplification status, grade stage, and DNA ploidy was observed in this small cohort, amplification was more noted in high grade, high stage, and aneuploid tumors. A highly statistical correlation between PRAD-1 amplification and proliferative activity was noted (P > 0.001). The results of this study indicate that PRAD-1 amplification appears to be a late event in the tumorigenesis of head and neck carcinoma and is associated often with a subset of aggressive tumors and high proliferation neoplasms.
Salivary duct carcinoma (SDC), a rare neoplasm of the major salivary glands, is a high-grade carc... more Salivary duct carcinoma (SDC), a rare neoplasm of the major salivary glands, is a high-grade carcinoma with a predilection for elderly men. The authors investigated the prognostic role of p53, c-erbB2, proliferating cell nuclear antigen (PCNA), and DNA flow cytometry in a pathobiological evaluation of a cohort of 30 patients with these neoplasms. The patient group comprised 24 men and 6 women, with ages ranging from 22 to 87 years (mean = 61 years). Twenty-eight tumors were located in the parotid gland and two in the submandibular gland. Tumor size ranged from 1.0 to 8.0 cm (mean = 3.48 cm). Regional metastases were found in 73.3% (22 patients), systemic metastases in 43.3% (13 patients), and recurrences in 8 (26.6%) patients. DNA aneuploidy was found in 18 tumors (58.0%) and DNA diploidy in 12 (42%), with proliferative fractions ranging from 8.60% to 15.5 (mean = 10.6%). p53 protein nuclear immunostaining was positive in 56.6% and c-erbB2 overexpression was observed in 63% of the tumors. PCNA positivity ranged from 16.5% to 91.0%, with a mean of 49.5%. p53 immunopositivity, DNA aneuploidy, high growth, and proliferative fractions by PCNA and flow cytometry did not correlate with patient outcome. These results indicate that tumor size (P = .05), distant metastasis (P = .006), and C-erbB2 amplification (P = .04) are independent prognostic parameters in patients with salivary duct carcinoma.
Abstract – A review of histologic classification systems for grading of malignancy in squamous ce... more Abstract – A review of histologic classification systems for grading of malignancy in squamous cell carcinomas of the head and neck region is presented. Reasons behind the varying results obtained in studies using his tomorphologic grading schemes are presented and potential errors involved in this type of clinical research are discussed. Requirements for the study of correlations between malignancy grade scoring, and recurrence and survival rates are presented. These include factors as patient selection, clinical staging, and follow-up principles. Special attention must be given to treatment modalities, establishment of negative surgical margins and occurrence of regional lymph node and/or distant metastases.
A 7 year follow-up of 120 patients with malignant parotid cancers revealed parotidectomy to be an... more A 7 year follow-up of 120 patients with malignant parotid cancers revealed parotidectomy to be an adequate procedure for low-grade, nonaggressive lesions. The addition of radiation therapy postoperatively will improve local and regional control of high-grade, aggressive lesions. Postoperative radiation therapy may also make the removal of the facial nerve unnecessary in certain clinical presentations.
p73 and p63 are recently cloned genes that share considerable structural and functional homologie... more p73 and p63 are recently cloned genes that share considerable structural and functional homologies with the p53 tumor suppressor gene. These genes, unlike p53, express multiple mRNA isoforms with variable biologic functions, and their suppressor nature has yet to be confirmed. To determine the interrelationship between these genes in the tumorigenesis of head and neck squamous carcinoma (HNSC), we performed immunohistochemical analyses of their protein products and compared the data with clinicopathologic parameters in 38 patients. In histologically normal epithelium, p53 and p73 showed similar basal and/or parabasal expression, but that of p53 was weaker and discontinuous. p63 staining was noted in more suprabasal cellular layers and was stronger. In dysplasias, all three markers manifested variable but gradual increase in extent and intensity of cellular expression with histologic progression. In carcinomas, p63 was the most frequently expressed (94.7%), followed by p73 (68.4%) and p53 (52.6%). Significant statistical correlation was noted only between p63 and p73 expressions (P =.04). Although no statistical correlation was found between p53 and p63 or p73, p53-negative tumors overexpressed either p63 or p73. p73 expression was associated with distant metastasis and perineural/vascular invasion. Our study indicates that (1) p63 and p73 expression may represent an early event in HNSC tumorigenesis, (2) the lack of correlation between p73 or p63 and p53 expression suggests an independent and/or compensatory functional role, (3) p73 expression may play a part in HNSC progression, and (4) p73 and p63 may function as oncogenes in the development of these tumors. HUM PATHOL 33:158-164. Copyright 2002, Elsevier Science (USA). All rights reserved.
In a continually renewing cell population, stem cells can be regarded as a reservoir of cells wit... more In a continually renewing cell population, stem cells can be regarded as a reservoir of cells with a high capacity for self renewal that give rise to all differentiated progeny. They are the primary source for the generation and maintenance of cellular diversity and tissue homeostasis. In general, neoplasms manifest differentiation pathways similar to those found in the development and renewal of the normal tissues from which they arise. This feature serves as a basis for classification schemes of neoplasms and, as in the normal tissues, there is usually an inverse correlation between proliferative capacity and differentiation within the neoplasms. In our postulate of the histogenesis of salivary gland neoplasia, we evoke the stem cell model to account for the considerable phenotypic heterogeneity seen with these neoplasms. We further consider the neoplasms and, in particular, their myoepithelial constituencies to be manifestations of escape from normal regulatory mechanisms that determine differentiation pathways which a stem cell and its progeny can take. Clinical and basic scientific evidence are presented to support the postulate and also to point to the mitigating role that myoepithelial differentiation has in the biological course of salivary gland neoplasms.
... 2 Head and Neck Surgery, The University of Texas, MD Anderson Cancer Center, Houston. *Corres... more ... 2 Head and Neck Surgery, The University of Texas, MD Anderson Cancer Center, Houston. *Correspondence: Mario A. Luna MD, Department of Pathology, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Publication History. ...
A clinico-pathologic study of 12 patients, each harboring a hitherto not delineated adenocarcinom... more A clinico-pathologic study of 12 patients, each harboring a hitherto not delineated adenocarcinoma of salivary origin is presented. The authors have designated this histologically unique carcinoma as 'terminal duct adenocarcinoma' in deference not only to its light-optic appearance, but also to a putative origin from the reserve cells (epithelial and myoepithelial) of the intercalated duct. The tumors' local invasive properties with extension into nerves and adjacent bone suggest their biologic behavior is like that of adenoid cystic carcinomas.
Salivary duct carcinomas of the major salivary glands have two major distinguishing features. The... more Salivary duct carcinomas of the major salivary glands have two major distinguishing features. They closely resemble ductal carcinomas of the breast and they are high-grade malignancies. In general, but particularly for carcinomas measuring three or more centimeters in size, the clinical course is one characterized by a resistance to local control, metastases to regional lymph nodes and distant sites, and death within a few years after primary surgical treatment.
Abnormalities in chromosome 11q13 regions have been frequently found in head and neck squamous ca... more Abnormalities in chromosome 11q13 regions have been frequently found in head and neck squamous carcinoma. Recent studies indicate that the PRAD-1 (also CCND1), which encodes cyclin D1, is a putative oncogene that is an important component of this region. DNA was extracted from 32 snap-frozen specimens from primary head and neck squamous carcinomas. DNA from peripheral blood lymphocytes, normal mucosa, and salivary gland tissue were used as controls. A genomic DNA probe containing the first exon of PRAD-1 was used for hybridization with specimen DNAs by the Southern technique. A 5.6-kb genomic DNA probe of immunoglobulin heavy chain was used as an internal standard for assessing PRAD-1 amplification. Eleven (34.4%) squamous carcinoma specimens showed PRAD-1 amplification (2- to 10-fold). Although no significant statistical correlation among amplification status, grade stage, and DNA ploidy was observed in this small cohort, amplification was more noted in high grade, high stage, and aneuploid tumors. A highly statistical correlation between PRAD-1 amplification and proliferative activity was noted (P > 0.001). The results of this study indicate that PRAD-1 amplification appears to be a late event in the tumorigenesis of head and neck carcinoma and is associated often with a subset of aggressive tumors and high proliferation neoplasms.
Salivary duct carcinoma (SDC), a rare neoplasm of the major salivary glands, is a high-grade carc... more Salivary duct carcinoma (SDC), a rare neoplasm of the major salivary glands, is a high-grade carcinoma with a predilection for elderly men. The authors investigated the prognostic role of p53, c-erbB2, proliferating cell nuclear antigen (PCNA), and DNA flow cytometry in a pathobiological evaluation of a cohort of 30 patients with these neoplasms. The patient group comprised 24 men and 6 women, with ages ranging from 22 to 87 years (mean = 61 years). Twenty-eight tumors were located in the parotid gland and two in the submandibular gland. Tumor size ranged from 1.0 to 8.0 cm (mean = 3.48 cm). Regional metastases were found in 73.3% (22 patients), systemic metastases in 43.3% (13 patients), and recurrences in 8 (26.6%) patients. DNA aneuploidy was found in 18 tumors (58.0%) and DNA diploidy in 12 (42%), with proliferative fractions ranging from 8.60% to 15.5 (mean = 10.6%). p53 protein nuclear immunostaining was positive in 56.6% and c-erbB2 overexpression was observed in 63% of the tumors. PCNA positivity ranged from 16.5% to 91.0%, with a mean of 49.5%. p53 immunopositivity, DNA aneuploidy, high growth, and proliferative fractions by PCNA and flow cytometry did not correlate with patient outcome. These results indicate that tumor size (P = .05), distant metastasis (P = .006), and C-erbB2 amplification (P = .04) are independent prognostic parameters in patients with salivary duct carcinoma.
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