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Biomedical subjects

Sathima Natarajan

Publications and source records attributed to Sathima Natarajan.

6 recordsLinked to original sources

Lymphovascular and perineural invasion in the parametria: a prognostic factor for early-stage cervical cancer.

OBJECTIVE: To estimate the impact of parametrial lymphovascular and perineural involvement on nodal metastasis and failure pattern of women with early-stage, surgically treated cervical cancer. METHODS: Clinical records and pathologic slides of 93 patients with early-stage cervical cancer (2 IA2, 52 IB1, 31 IB2, and 8 IIA) treated with radical hysterectomy and pelvic lymphadenectomy with or without paraaortic lymphadenectomy were reviewed. The study group comprised 80 patients with squamous cell carcinoma and 13 patients with adenocarcinoma of the cervix. Median follow-up time was 33 months. The association among the various histopathologic predictors of outcome was determined with chi2 analysis. The influence of the predictors on outcome was examined with log rank survival methods and the Cox regression model. RESULTS: The presence of parametrial lymphovascular space invasion is a predictor of disease in the pelvic (P<.001) and paraaortic (P<.05) lymphatics independently. Large tumor size (greater than 4 cm), parametrial perineural invasion, cervical lymphovascular space invasion, and tumor depth (greater than two thirds) were found to be simultaneous predictors of recurrence on multivariate analysis (P<.05). Using these four binary predictor variables, we have computed a model-based relative risk. Based on this model, the presence of perineural invasion in the parametria more than doubles the risk of recurrence in the cohort of patients with large (greater than 4 cm) tumors (P<.05). In a subset analysis of patients with negative nodal disease, parametrial perineural invasion and tumor size were independent predictors of poor outcome (P<.05). CONCLUSION: Presence of parametrial lymphovascular space invasion correlates significantly with the risk of nodal metastasis in women with early-stage cervical cancer. Parametrial perineural invasion is an independent poor prognostic factor. Histopathologic findings within the parametria are a valuable independent predictor of recurrence and thus may influence the selection of patients for adjuvant treatment.

Adenocarcinoma↗

Urokinase plasminogen activator receptor: Prognostic biomarker for endometrial cancer.

Endometrial adenocarcinoma is the most common gynecologic malignancy in the United States. However, reliable diagnostic or prognostic tumor markers have not been identified for endometrial cancer. In this study, we examined whether urokinase plasminogen activator receptor (UPAR), a glycosyl-phosphatidylinositol-linked membrane protein, is a candidate diagnostic or prognostic marker for patients with cancer of the endometrium. Sixty-five surgically excised, formalin-fixed endometrial tissue specimens were accessioned through the Department of Pathology Registry at the University of California, Los Angeles, and analyzed for UPAR expression by using immunohistochemical techniques. A retrospective review was also performed to determine stage and histopathologic grade of disease, recurrence, and mortality. No expression of UPAR protein was present in seven patients with benign neoplasia of the endometrium. UPAR protein expression highly correlated with stage of disease (ungrouped Spearman correlation = 0.625, P < 0.0001): 40% of patients with stage I, 66% of patients with stage II, 100% of patients with stage III, and 85% with stage IV demonstrated the highest level of UPAR expression. Moreover, high UPAR expression positively correlated with grade of disease (ungrouped Spearman correlation = 0.71, P < 0.0001): 29% of grade 1 specimens, 57% of grade 2, and over 90% of specimens with grade 3, the majority representing uterine papillary serous carcinoma and mixed malignant mesodermal tumor. Finally, UPAR protein expression also positively correlated with rate of recurrence and mortality in patients with adenocarcinoma of the endometrium (ungrouped P = 0.034). Our data suggest that UPAR is a useful prognostic marker for biologically aggressive forms of endometrial cancer.

Adenocarcinoma↗

Familial mutation in the testis-determining gene SRY shared by an XY female and her normal father.

In humans, mutations in the testis-determining gene SRY result in XY sex reversal with pure gonadal dysgenesis (PGD). However, only about 10-15% of the cases of PGD can be explained by mutations within the SRY open reading frame, suggesting the existence of other sex-determining genes. Although SRY is known to bind and bend DNA, its target and mode of action remain elusive. Here, we describe a novel mutation in SRY at codon 127, resulting in a tyrosine (Y) to phenylalanine (F) substitution in the protein. This sequence variant was found not only in the XY female patient but also in her father, who is a phenotypically normal male. However, this Y127F variant was not found in the SRY sequences of 93 other randomly chosen males. This substitution affects a highly conserved tyrosine residue in the HMG box of SRY, in which two de novo mutations have been described previously in XY females with PGD. Furthermore, electromobility shift studies demonstrate that SRY protein harboring the Y127F variant is incapable of binding consensus SRY binding sites in vitro. Taken together, these data suggest that the Y127F variant is a novel mutation with functional consequences and not simply a polymorphism. The allelic variant of SRY transmitted in this family and shared by both a phenotypic female (proband) and a phenotypic male (proband's father) emphasizes the importance of modifier genes in the sex determination pathway.

Amino Acid Substitution↗

Simultaneous occurrence of medullary and papillary carcinoma of the thyroid gland identified by fine needle aspiration. A case report.

BACKGROUND: Fine needle aspiration (FNA) diagnosis of simultaneous medullary and papillary thyroid carcinoma in independent thyroid lobes is exceedingly rare. CASE: A 36-year-old female presented with a one-month history of dysphagia. Thyroid ultrasound revealed a multinodular goiter. She was clinically and biochemically euthyroid. FNA of the right thyroid nodule was consistent with medullary carcinoma, and FNA of the left thyroid lobe was consistent with papillary carcinoma. Immunohistochemistry revealed strong calcitonin and CEA positivity in the right lobe and lack of staining in the left lobe. Conversely, staining for thyroglobulin was negative on the right lobe and positive on the left lobe. CONCLUSION: The patient developed tumors in separate lobes of the thyroid. Immunoreactivity of calcitonin, CEA and thyroglobulin made a sharp distinction between the two tumors. Therefore, we conclude that these tumors were not linked by either embryology or genetics.

Adult↗