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Manju L Prasad

Publications and source records attributed to Manju L Prasad.

13 recordsLinked to original sources
PubMed2005

MSG-1 expression in benign and malignant melanocytic lesions of cutaneous and mucosal epithelium.

BACKGROUND: A more recently characterized melanocyte-specific gene, MSG-1, has been suggested as having a role in embryogenesis, melanogenesis and melanoma progression. Studies involving MSG-1 have involved cutaneous melanocytic lesions, which are different than non-cutaneous melanocytic lesions in certain pathogenetic aspects. The purpose of this study was to evaluate MSG-1 protein expression in cutaneous and mucosal melanocytic lesions, with the aim to explore its association with pigment production, malignant potential and UV light exposure. MATERIAL/METHODS: Benign and malignant melanocytic lesions of cutaneous and mucosal epithelium were selected from our pathology registry (n=48). Immunohistochemistry was performed using polyclonal anti-MSG-1 antibody and standard streptavidin-biotin immunoperoxidase techniques. The staining pattern of MSG-1 was evaluated by three pathologists independently. RESULTS: MSG-1 protein demonstrated immunoreactivity in only one mucosal melanoma (1/20, 5%), arising in the lower lip, and showing histopathologic evidence of sun-induced tissue damage. MSG-1 also showed positivity in five cutaneous melanomas (5/14, 36%), one of which was a metastatic lesion. All mucosal and cutaneous nevi failed to express MSG-1. Melanin pigmentation, seen in 18/34 melanoma and 13/14 nevi, did not correlate with MSG-1 expression. All cases but one showing MSG-1 immunoreactivity were located in sun-exposed sites. CONCLUSIONS: The finding of MSG-1 expression in some cases of malignant melanoma, and its absence in all benign nevi, may indicate an association with melanoma progression, particularly UV-induced lesions. Its infrequent expression in melanocytic lesions limits its diagnostic value as an immunohistochemical marker in routine pathology practice.

Adult↗
PubMed2005

Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors.

The diagnosis of thyroid tumors is critical for clinical management; however, tumors with follicular architecture often present problems. We evaluated the diagnostic use of the protein expression of four genes that were found to be upregulated in papillary thyroid carcinoma compared to normal thyroid (LGALS3, FN1, CITED1 and KRT19), and of the mesothelial cell surface protein recognized by monoclonal antibody HBME1 in thyroid tumors. Tissues from 85 carcinomas (67 papillary, six follicular, eight Hürthle cell and four anaplastic) and 21 adenomas were evaluated by immunohistochemistry for the expression of these gene protein products, for example, galectin-3 (GAL3), fibronectin-1 (FN1), CITED1, cytokeratin-19 (CK19) and HBME1. Non-neoplastic thyroids (29 adenomatous and 14 thyrotoxic hyperplasia, and 59 normal) were also studied. The expression of all five proteins was significantly associated with malignancy, and highly specific (> or = 90%) for carcinoma compared to adenoma. GAL3, FN1 and/or HBME1 expression was seen in 100% of carcinomas (85/85) and in 24% of adenomas (5/21). Coexpression of multiple proteins was seen in 95% of carcinomas and only 5% of adenomas (P<0.0001). Coexpression of FN1 and GAL3 (FN1+ GAL3+, 70/85) or FN1 and HBME1 (FN1+ HBME1+, 53/85) was restricted to carcinomas, while their concurrent absence (FN1- GAL3- or FN1- HBME1-, 18/21 adenoma) was highly specific (96%) for benign lesions. Among non-neoplastic thyroids, adenomatous hyperplasia frequently expressed GAL3 (n=16), CK19 (n=9) and CITED1 (n=7), but the expression was predominantly focal in contrast to the diffuse expression in carcinomas. An immunohistochemical panel consisting of GAL3, FN1 and HBME1 may be useful in the diagnosis of follicular cell-derived thyroid tumors.

Adenoma↗
PubMed2005

Allelic variation in gene expression in thyroid tissue.

Heritable allelic variation in gene expression may contribute to sporadic and familial disease, but is relatively unexplored. Papillary thyroid cancer (PTC) is characterized by strong heritability but predisposing genes have not been detected. Here we tested the hypothesis that inherited variation in allelic expression occurs in thyroid tissue and so might contribute to disease. We studied genes with a role in thyroid function, signaling, and/or tumorigenesis (PRKAR1A, DUOX1, IP3RI, ARGBP2, TPO, TG, and PEG10). We screened thyroid tissues from controls and patients with thyroid disease and lymphoblastoid cell lines from 40 healthy individuals. We demonstrated the robustness of the technique, a fluorescent dideoxy terminator-based method distinguishing the mRNA products of alleles in individuals who are heterozygous for a polymorphism in the transcript. We confirmed that the PEG10 gene transcript was derived only from one allele because of genetic imprinting. Three other genes, DUOX1, TPO, and ARGBP2 showed allelic variation in thyroid tissue and/or lymphoblastoid cells. Benign and malignant thyroid tissue from the same patient always gave concordant results. DUOX1 variation in expression was seen in 3 of 13 patients with PTC and 6 of 27 patients with benign disease. Further studies are needed to determine the significance of these and other allelic variations.

Alleles↗
PubMed2005

Variable expression of coxsackie-adenovirus receptor in thyroid tumors: implications for adenoviral gene therapy.

Adenoviral gene therapy represents a novel approach for the treatment of aggressive thyroid carcinomas. Both coxsackie-adenovirus receptor (CAR) and integrins have been shown to be the major determinants for adenoviral infectivity in many types of cancer cells, yet conflicting results have been reported. In this report we examine these factors mediating adenoviral infection in thyroid cells and to evaluate CAR expression in various types of thyroid cancer. We found that neither expression levels of CAR nor integrins are solely predictive of adenoviral infectivity in thyroid cells. However, the absence of CAR was associated with poor adenoviral infectivity in immortalized rat FRTL-5 cells. Moreover, preincubation with alpha-CAR antibody decreased infectivity in FTC 238 cells, a human thyroid tumor line. These results indicate that CAR does play a role in adenoviral infection of thyroid cells. Immunohistochemical analysis revealed that CAR is expressed at the cell surface in the majority of malignant thyroid tumors. We further show that adenoviral infectivity in some thyroid cancer cells can be improved by poly-L-lysine. Our study warrants a functional method to evaluate adenoviral infectivity should be developed and instituted prior to clinical trials of adenoviral gene therapy in patients with advanced thyroid cancer.

Adenoviridae↗
PubMed2004

Primary mucosal melanoma of the head and neck: a proposal for microstaging localized, Stage I (lymph node-negative) tumors.

BACKGROUND: The current study was conducted to identify histologic predictors of survival in patients with localized, lymph node-negative (Stage I, N0M0) primary mucosal melanomas of the head and neck (HNMM). METHODS: The histology of 39 sinonasal, 20 oral, 1 pharyngeal, and 1 laryngeal Stage I HNMM was reviewed by 2 pathologists without knowledge of patient outcome. The invasion was evaluated as Level I: melanoma in situ (without invasion or with microinvasion only); Level II: invasion into the lamina propria only; and Level III: invasion into deep tissue (e.g., skeletal muscle, bone, or cartilage). The tumor architecture was defined as pseudopapillary when tumor cells clustered around blood vessels resembling papillae and sarcomatoid when they resembled high-grade pleomorphic sarcoma. Survival analysis was performed with Kaplan-Meier survival curves using disease-specific survival (DSS) as the endpoint. RESULTS: The 5-year DSS rate was 43% (median, 41.5 months). The median survival was found to decrease significantly with increasing level of invasion: Level I (n = 4): 138 months; Level II (n = 29): 69 months; and Level III (n = 28): 17 months (P = 0.003). The presence of pseudopapillary and sarcomatoid architecture (n = 20) and undifferentiated cells (n = 16) were found to be associated with a significantly poor DSS (P < 0.05). However, on multivariate analysis, only the level of invasion remained an independent predictor of survival (P = 0.03). Tumor thickness, vascular invasion, and necrosis were found to have no significant influence on survival. CONCLUSIONS: Microstaging according to invasion into three tissue compartments was found to be a significant and independent predictor of poor survival in patients with localized, lymph node-negative, Stage I HNMM. The presence of sarcomatoid and pseudopapillary architecture and undifferentiated cells also appear to be associated with significantly poor DSS.

Adult↗
PubMed2004

Primary mucosal desmoplastic melanoma of the head and neck.

BACKGROUND: Desmoplastic variants of melanoma rarely affect the mucosa. METHOD: The clinicopathologic features and p53 status of seven primary mucosal desmoplastic melanomas of the oral and nasal cavity were studied. RESULTS: The patients included six men and one woman (median age, 61 years; range, 23-74 years). Desmoplastic melanoma involved the lip in two, alveolus in three, buccal mucosa in one, and nasal vestibule in one patient. Four tumors infiltrated up to lamina propria, and three infiltrated bone and/or cartilage. All were amelanotic spindle cell tumors, five were neurotropic, and two were vasoinvasive. Aberrant p53 expression was seen in six tumors. All tumors recurred locally, and distant metastasis developed in three. Six patients died with disease (survival, 1-41 years; median, 8 years), and one patient was free of disease (survival 20 years). CONCLUSIONS: Primary mucosal desmoplastic melanomas are clinically characterized by local recurrence and may lead to distant metastasis and death even after several years. Alterations in p53 expression are frequently associated with desmoplastic melanoma.

Adult↗
PubMed2004

Expression and significance of cancer testis antigens in primary mucosal melanoma of the head and neck.

BACKGROUND: Cancer testis antigens (CTAs) are T-cell-defined tumor-associated antigens encoded by the genes and gene families such as MAGE, NY-ESO-1, and others. Their expression in a wide variety of malignant neoplasms but absence in all normal adult tissue except testicular germ cells makes them attractive targets for immunotherapy of cancer. Primary mucosal melanomas of the head and neck (HNMM) are rare aggressive malignant tumors that are usually difficult to treat. CTAs may provide useful targets for therapy; however, their expression in HNMM is not known. METHODS: We analyzed 40 initial, 15 recurrent, and 15 metastatic HNMM to nonmucosal locations from 64 patients (oral, n = 30; sinonasal, n = 34). Immunohistochemistry was performed on archival tissue with monoclonal antibodies 57B, CT7-33, and ES121 to the following CTAs: MAGE-A4, CT7 (MAGE-C1), and NY-ESO-1, respectively. RESULTS: CT7, MAGE-A4, and NY-ESO-1 expression was seen in 73%, 61%, and 24% of tumors, respectively, with 81% of the tumors expressing at least one of the CTAs. CT7 and MAGE-A4 were significantly more frequently expressed in tumors composed of epithelioid cells than spindle cells (p = .05). CTA expression did not correlate with disease progression, overall survival, and disease-specific survival. CONCLUSIONS: CT7, MAGEA4, and NY-ESO-1 are frequently expressed in HNMM and may be potential targets for CTA-based immunotherapy. The expression does not seem to have prognostic significance.

Aged↗
PubMed2004

CITED1 protein expression suggests Papillary Thyroid Carcinoma in high throughput tissue microarray-based study.

Molecular markers of papillary thyroid carcinoma (PTC) are relatively unknown. Recently, the CITED1 gene was reported to be greatly upregulated in PTC relative to normal thyroid. The CITED1 protein, a 27-kd transcriptional transactivator nuclear protein is expressed in PTC, melanocytes, breast epithelial cells, and several embryonic tissues. However, its expression in other thyroid masses and non-thyroid tumors is not known. We evaluated CITED1 protein expression in tissue microarrays comprising various thyroid and nonthyroid tissues by immunohistochemistry using a polyclonal anti-CITED1 antibody. CITED1 expression was seen in 63 of 68 PTC (93%), 3 of 12 follicular carcinomas (25%), 2 of 7 Hürthle cell carcinomas (28%), 2 of 21 adenomas (10%), 2 of 6 follicular neoplasms of undetermined malignant behavior (33%), and 2 of 24 nodular goiters (8%). Normal thyroids (n = 27), thyrotoxic hyperplasias (n = 14), and anaplastic thyroid carcinomas (n = 5) did not express CITED1. Among nonthyroid tumors, 6 of 23 melanomas (26%), 11 of 65 prostatic carcinomas (17%), 3 of 25 glioblastomas (12%), 4 of 67 breast carcinomas (6%), 1 of 49 lymphomas (2%), 1 of 65 lung carcinomas (2%), 1 of 68 colon carcinomas (2%), and none of 49 ovarian carcinomas (0%) expressed CITED1. The accuracy of CITED1 in differentiating PTC from benign thyroid nodules, other thyroid carcinomas, and nonthyroid carcinomas was 93%, 89%, and 94%, respectively. CITED1 is preferentially expressed in PTC and may be used as a diagnostic marker of it.

Adenocarcinoma, Follicular↗
PubMed2003

Clinicopathologic differences in malignant melanoma arising in oral squamous and sinonasal respiratory mucosa of the upper aerodigestive tract.

OBJECTIVE: Primary mucosal melanomas are rare tumors. We compare melanomas arising in 2 histologically different mucosa, the stratified oral squamous mucosa and pseudostratified sinonasal respiratory mucosa, to investigate the clinicopathologic influence of native mucosal histology on the tumor. METHODS: Clinicopathologic features of 36 melanomas arising in the squamous mucosa of the oral cavity were compared with 59 melanomas arising in the sinonasal respiratory mucosa. RESULTS: The median age of patients was 61 and 63 years for oral and sinonasal melanomas, respectively, with the squamous and respiratory mucosa covering the maxilla being most frequently involved (68.7% and 66%, respectively). The former had a remarkable male predilection (28 men, 8 women), while the latter affected both sexes equally (29 men, 30 women). The oral melanomas were more likely to be detected in the early in situ or microinvasive stage (4 cases vs none, P =.008) and were more frequently amelanotic (14 vs 12, P =.049) than sinonasal melanomas. The sinonasal melanomas were frequently thicker (median thickness, 9 vs 2.6 mm), polypoid (29 vs none), ulcerated (57 vs 20), and necrotic (57 vs 14) than oral melanoma (P <.001). Pseudopapillary architecture was more frequent in sinonasal melanomas (16 tumors vs none, P <.001), and desmoplastic melanomas were more frequent in the oral mucosa (6 vs 1, P =.005). Sinonasal melanoma showed vascular and deep tissue invasion more frequently than oral melanoma; however, no significant difference in disease-specific survival was noted (median survival, 2.8 years vs 3.0 years; 5-year survival, 37% vs 35%, respectively). CONCLUSION: Sinonasal melanomas demonstrated aggressive morphologic features significantly more frequently than oral melanomas; however, prognosis remained similar in both groups.

Adult↗
PubMed2002

Primary mucosal malignant melanoma of the head and neck.

INTRODUCTION: The relative rarity of mucosal melanomas of the head and neck (MMHN) has made analysis of treatment approaches difficult. Advances in diagnostic techniques and treatment interventions have had obvious impact on outcomes in cutaneous melanoma, but the effects on outcome in MMHN remain undefined. This study aims to assess the outcome and identify clinical and histologic prognostic indicators in a recent cohort of patients with MMHN treated at a single institution. METHODS: The clinical records of 59 patients with the diagnosis of MMHN treated at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1978 and 1998 were retrospectively reviewed. Pathologic material on each of these patients was prospectively reviewed by at least two pathologists (MP, KB, or AH) for confirmation of diagnosis and assessment of histologic variables. Survival was calculated by the Kaplan-Meier method. Clinical (patient demographics, tumor characteristics, and treatment) and histologic data (tumor thickness, melanosis, melanoma in situ, vascular invasion, and multifocality) were analyzed for impact on outcome by both univariate and multivariate analyses. RESULTS: Thirty-five patients (59%) had sinonasal tumors (SNMM), whereas 24 (41%) had oral (ORMM) tumors. Forty-seven patients (79.6%) were staged as stage I, 8 (13.6%) as stage II, and 4 (6.8%) were classified as stage III. Regional lymphatic metastases at presentation were more frequent in ORMM compared with SNMM (25% vs 6%, p =.05). Surgery was used in all patients. Adjuvant radiation therapy was used more frequently in the SNMM group compared with the ORMM group (40% vs 17%, p =.04). The rates of local failure for ORMM and SNMM were 51% and 50%, nodal failure rates were 42% and 20%, and distant failure rates were 67% and 40%, respectively (p = NS). With a median follow-up of 20 months, the 5-year disease-specific survival rate was 44% (40% for ORMM vs 47% for SNMM, p = NS). Significant prognostic factors for disease-specific survival on univariate analysis included advanced clinical stage at presentation, tumor thickness greater than 5 mm, presence of vascular invasion, and development of nodal and distant metastases. On multivariate analysis, however, regional nodal failure lost significance. CONCLUSIONS: Clinical stage at presentation, tumor thickness greater than 5 mm, vascular invasion on histologic studies, and development of distant failure are the only independent predictors of outcome in MMHN.

Adult↗
PubMed2002

Intraoral presentation of Rosai-Dorfman disease: a case report and review of the literature.

Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy, is an unusual clinical entity. It classically presents with massive cervical lymphadenopathy, but atypical presentations have been described in the absence of nodal involvement, making diagnosis difficult. We report a case that presented with isolated involvement of the maxillary alveolus and discuss the diagnostic dilemmas and approaches to management in patients with atypical clinical features.

Adult↗
PubMed2002

Prognostic factors for malignant melanoma of the squamous mucosa of the head and neck.

Primary malignant melanomas of the squamous mucosa of the head and neck are rare. To learn more about the prognostic significance of various histologic parameters we examined the pathologic features of squamous mucosa from 40 patients seen at a single institution and correlated them with clinical outcome. Follow-up information was available on 37 patients. Thirty-five were treated with surgical resection and two were treated with radiotherapy. Twenty-six were dead at follow-up. Twenty-one of them died of disease. The interval between diagnosis and death ranged from 1 month to 16.5 years (median survival, 2.4 years). Eleven patients were alive at 4 months to 19.5 years after the diagnosis: six of them with disease and five of them free of disease (mean follow-up, 3.5 years). Predictors of poor survival by univariate analysis were the presence of vascular invasion (overall survival, p = 0.007; disease-specific survival, p = 0.01), a polymorphous tumor cell population (overall survival, p = 0.007; disease-specific survival, p = 0.008), and necrosis (overall survival, p = 0.007; disease-specific survival, p = 0.056). However, because these three parameters were associated with each other, none of them remained of independent predictive value for outcome by multivariate analysis. No prognostic significance was found for tumor thickness, level of invasion, ulceration, mitotic index, or nerve/nerve sheath involvement. Thus, the histologic parameters relevant for the prognosis of squamous mucosa differ significantly from those of cutaneous melanomas.

Adult↗