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Biomedical subjects

J G Batsakis

Publications and source records attributed to J G Batsakis.

At least 73 records · Page 4Linked to original sources

Amplification and overexpression of HER-2/neu in carcinomas of the salivary gland: correlation with poor prognosis.

There are few reliable prognostic markers of biological aggressiveness for head and neck carcinomas in general. For salivary gland carcinomas, anatomic location, tumor size, histological grade, and extent of disease involvement are considered to be clinically important risk factors for recurrent disease. Molecular genetic alterations in salivary gland carcinomas have not been characterized, and tumor cell proteins have not been shown to be prognostically significant. Here a cohort of mucoepidermoid carcinomas of the major (parotid and submandibular) salivary glands are analyzed for a molecular genetic alteration, HER-2/neu gene amplification, and gene amplification and expression results are compared with long-term clinical follow-up information. Archival tissues resected from 58 patients with mucoepidermoid carcinoma of salivary glands were evaluated for HER-2/neu gene amplification by fluorescence in situ hybridization and for gene expression by immunohistochemistry in a blinded fashion. Clinical follow-up information was compared with the results of these analyses to determine whether there were significant associations. Overexpression, identified as membrane immunostaining by immunohistochemistry, was observed in 22 of 58 (38%) mucoepidermoid carcinomas. Gene amplification, characterized by fluorescence in situ hybridization, was observed in 12 (21%) cases. Eleven of the 12 cases with gene amplification were also immunostained for HER-2/neu. Both gene amplification (P = 0.0001, P < 0.0001) and immunostaining (P < 0.0001, P < 0.0001) were correlated with shorter disease-free interval and poorer overall patient survival, respectively. Multivariate analysis showed that HER-2/neu immunostaining and amplification were markers of poor prognosis independent of histopathological grade, tumor size, and involvement of regional lymph nodes. HER-2/neu is amplified and/or overexpressed in approximately one-third of mucoepidermoid carcinomas of salivary glands. Amplification and/or overexpression appears to be an independent marker of poor prognosis in mucoepidermoid carcinomas of the salivary glands as it is in carcinomas of the breast, ovary, and endometrium.

Adolescent↗

PRAD-1 (CCND1)/cyclin D1 oncogene amplification in primary head and neck squamous cell carcinoma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Aneuploidy↗

Trisomy 5 as the sole chromosomal abnormality in a primary mucoepidermoid carcinoma of the minor salivary gland.

We describe the cytogenetic findings in a moderately differentiated primary mucoepidermoid carcinoma of the base of the tongue. The only karyotypic abnormality found in the primary culture of this neoplasm was trisomy 5. This finding is remarkably different from previous cytogenetic studies of mucoepidermoid carcinomas, which have shown heterogeneous and unrelated chromosomal aberrations. Our results suggest that trisomy 5 may be an early aberration in the development of this neoplasm.

Carcinoma, Mucoepidermoid↗

Prognostic factors in mucoepidermoid carcinomas of major salivary glands: a clinicopathologic and flow cytometric study.

Mucoepidermoid carcinomas (MEC) of the major salivary glands from 48 patients who received their treatment at a single institution were studied for prognostic indicators. Uni- and multivariate statistical analyses were performed on several clinicopathologic factors and also on flow cytometric (FCM) DNA content data of the carcinomas. Clinical prognostic factors associated with decreased survival included age > 60 years (P = 0.01), male gender (P = 0.002), symptoms at diagnosis (P = 0.03), stage of disease (P < or = 0.0001), type of surgery (P = 0.0006), and recurrence (P = 0.0001). Histopathological prognostic factors associated with decreased survival included MEC tumour grade (P = 0.0001), tumour size > 3.0 cm (P = 0.02), lymph node involvement (P = 0.0004) and positive surgical margins (P = 0.007). DNA FCM factors associated with decreased survival included aneuploid tumours (P = 0.08) and proliferative activity (S+G2M > 5%, P = 0.07). Multivariate analysis indicated that histological grade, proliferative activity, symptoms at diagnosis, clinical stage of disease and type of surgery were significant (P < or = 0.05) prognostic/survival factors in the biological assessment of this neoplasm.

Adolescent↗

Staging of salivary gland neoplasms: role of histopathologic and molecular factors.

Cancer is a disease of altered cellular genes. These altered genes, in turn, produce the malignant phenotype by inducing changes in proliferation and differentiation during the cell cycle. The changes can be assessed by techniques to measure proliferation and by histologic grading to distinguish levels of differentiation. Since proliferation factors and differentiation end points reflect the net effect of genetic damage and include, therefore, the accumulated changes in genes, they more aptly qualify as potential prognostic indicators than do individual oncogene alterations. By using mucoepidermoid carcinoma of the major salivary glands as the test model, I strongly suggest that a reproducible (three-tiered) grading system and measurements of proliferation (nuclear markers: proliferating cell nuclear antigen and, possibly, Ki-67; and proliferation fraction as determined by flow cytometry) can serve as cellular/molecular factors worthy of inclusion in existing clinical staging systems of salivary gland neoplasms.

Biomarkers, Tumor↗

Desmoplastic melanoma.

Desmoplastic melanoma is an uncommon type of malignant melanoma that has a predilection for the skin of the head and neck. Because of a progressive metaplasia of melanocytes and an accompanying desmoplasia, the neoplasm can be mistaken for benign or malignant soft tissue lesions. The neurotropism exhibited by many desmoplastic melanomas is a strong adverse factor for prognosis; otherwise, the biologic behavior is not unlike that of conventional melanomas.

Adult↗

Aneurysmal bone cysts of the jaws.

Aneurysmal bone cysts of the jaws are histologically the same as those found in the more usual appendicular sites for this lesion. They may be primary or secondary (associated with another definable osseous lesion) and have a 2:1 or 3:1 predilection for the mandible over the maxilla. Curettage is associated with relatively high recurrence rates, while surgical excision, with negative margins, of primary lesions markedly reduces this incidence.

Adolescent↗

Salivary duct carcinoma.

Salivary duct carcinoma is a high-grade neoplasm associated primarily with the parotid gland. Its abysmal prognosis demands aggressive clinical management. Initially named after its resemblance to intraductal carcinoma of the breast, this entity derives its histogenesis from the excretory duct reserve cells, which are also the source of origin of other biologically high-grade neoplasms. As this is a lesion seldom encountered by the clinician, it is important for the pathologist to clearly make the distinction between this malignancy and more indolent neoplasms, such as terminal duct adenocarcinoma.

Carcinoma↗

Extra-abdominal desmoid fibromatosis.

Desmoid fibromatosis cannot be considered a biologically benign or innocuous lesion. In the head and neck it may be intraosseous (desmoplastic fibroma) or, more often, in soft tissues, with the highest incidence in the supraclavicular region of the neck. High recurrence and persistence rates, 50% or more, accompany intralesional or marginal excision. Keloids and proliferative scars, while stubborn in their resolution and potentially disfiguring, are reactive proliferative disorders of fibroblastic and myofibroblastic tissues.

Bone Neoplasms↗

Granular cell tumors.

The skin and subcutaneous tissue and mucosae of the head and neck are areas of predilection for granular cell tumors. These often histogenetically enigmatic lesions have two principal clinicopathologic presentations: an infantile (congenital) epulis form of the gnathic gingiva and a noncongenital soft tissue and aerodigestive form. Recurrences of either form are largely attributable to marginal excision and, for all sites, approach 15%. A malignant granular cell tumor is recognized, but requires rigorous histologic confirmation.

Age Factors↗

Lichen planus and lichenoid lesions of the oral cavity.

Lichen planus is a mucocutaneous disease of unknown cause that has its principal clinical manifestations in the skin and mucosa of the oral cavity. The natural history of the cutaneous form is one of spontaneous resolution over time, while oral lichen planus pursues a much more chronic course with a low order of resolution. Oral lichen planus must be distinguished from lichenoid lesions, including lichenoid dysplasia. Malignant change in oral lichen planus is rare and is prompted by carcinogenic cofactors. There is no increased risk of development of carcinoma in cutaneous lichen planus.

Carcinoma, Squamous Cell↗

Pseudosarcomatous proliferative lesions of soft tissues.

The pseudosarcomatous proliferative lesions of soft tissues are fascia-based fibroblastic and myofibroblastic lesions that have the potential to be overdiagnosed as sarcomas. They may be subtyped according to depth of involvement, age at presentation, and certain histologic features. Subtypes are proliferative fasciitis, proliferative myositis, nodular fasciitis, intravascular fasciitis, and cranial fasciitis. They are presumed to be reactive. Recurrences are rare after tissue-sparing surgical excision.

Diagnosis, Differential↗

Proliferative verrucous leukoplakia and verrucous hyperplasia.

Proliferative verrucous leukoplakia and hyperplasia are irreversible clinicopathologic lesions of the oral cavity and upper respiratory tract with considerable potential for evolving into verrucous or other forms of squamous cell carcinoma. Proliferative verrucous leukoplakia is a disease of the oral cavity in which verrucous hyperplasia is a part of its developmental spectrum. Verrucous hyperplasia, at other head and neck mucosal sites, may be associated with papillomas or be a de novo lesion. Human papillomavirus, as a cofactor, plays a role in some of the lesions. In the instance of verrucous hyperplasia, the authors consider it an early form of verrucous carcinoma and recommend it be treated accordingly.

Aged↗

Hyalinizing clear cell carcinoma of salivary origin.

The recently described hyalinizing clear cell carcinoma of salivary tissues joins other clinicopathologic entities in its segregation from the formerly nondescript and heterogeneous classification "clear cell neoplasms." The carcinoma is preponderantly an intraoral (palate and base of tongue) neoplasm that is always infiltrative and capable of regional lymph node metastasis. To date, it has responded to locoregional control treatments and has not been life-consuming.

Adenocarcinoma, Clear Cell↗

Two perplexing skin tumors: microcystic adnexal carcinoma and keratoacanthoma.

Microcystic adnexal carcinoma and keratoacanthoma have a marked predilection for the skin of the head and neck. The adnexal carcinoma continues to be underrecognized, and the consequences for the patient are locally aggressive recurrences. The keratoacanthoma, on the other hand, may be inappropriately overdiagnosed, causing squamous cell carcinoma of the skin to be missed. In the instance of the solitary keratoacanthoma a conservative complete excision is recommended.

Adult↗

Sinonasal lymphomas.

Advances in immunocytochemical phenotyping and molecular genetics have nearly resolved the histopathologic and therapeutic quandaries brought about by a diagnostic nomenclature that provided little guidance in the management of midfacial necrotizing lesions. Gone are terms like midline granuloma syndrome, lethal midline granuloma, polymorphic reticulosis, lymphomatoid granulomatosis, midline destructive granuloma, and idiopathic midline destructive disease. They have been replaced by the appreciation that the majority of the lesions are lymphomas of the sinonasal tract. The lymphomas are of B- or T-cell lineage and have a broad biologic spectrum from low to high grade. Still to be addressed are apparent geographic differences in biologic behavior, the epidemiologic significance of a preponderance of T-cell nasal lymphomas in the Orient, and optimum therapeutic regimens.

Humans↗

High correlation with survival of proliferating cell nuclear antigen expression in mucoepidermoid carcinoma of the parotid gland.

We tested the hypothesis that proliferating cell nuclear antigen can predict survival in patients with mucoepidermoid carcinoma. Formalin-fixed, paraffin-embedded, tissue resected specimens from 43 patients with no prior treatment for mucoepidermoid carcinoma of the parotid gland were immunostained with the PC10 monoclonal antibody to proliferating cell nuclear antigen with the peroxidase/antiperoxidase method. Proliferating cell nuclear antigen levels were defined as the number of nuclei with strong immunostaining divided by the total cell count and were expressed as percentages. Both univariate and multivariate analyses were performed on 12 additional prognostic variables to determine the relative proliferating cell nuclear antigen level to predict survival. The median proliferating cell nuclear antigen level was 7. Five percent of patients with proliferating cell nuclear antigen levels less than 7 died of their disease compared with 48% of those with proliferating cell nuclear antigen levels of 7 or more. Multivariate analysis indicates proliferating cell nuclear antigen to be the most important parameter in predicting survival. Thus the measurement of proliferating cell nuclear antigen is a useful predictor of survival for patients with mucoepidermoid carcinoma of the parotid gland.

Adolescent↗