Circulating thyrotropin receptor messenger RNA for evaluation of thyroid nodules and surveillance of thyroid cancer in children

PurposeThe aim of this study was to determine the role of thyrotropin receptor messenger RNA as a novel blood test for evaluation of thyroid nodules and cancer in children.MethodsWe reviewed thyroid disease management of patients younger than 18 years with thyrotropin receptor messenger RNA measurements identified from a prospective, institutional review board-approved registry during 2008 to 2010.ResultsThirty-nine thyrotropin receptor messenger RNA measurements were made in 21 female patients (12-17 years old; median, 16 years). Four patients with fine-needle aspiration only had benign thyroid cytology, and 3 of 4 had undetectable thyrotropin receptor messenger RNA. Seventeen patients underwent 22 thyroid operations. Preoperative thyrotropin receptor messenger RNA was measured in 9 patients: 3 of 4 with thyroid cancer had elevated levels and 3 of 5 with goiters undetectable. Postthyroidectomy surveillance (median, 16 months; range, 6-24) of 11 thyroid cancer patients (8 papillary, 3 follicular) showed that thyrotropin receptor messenger RNA was concordant with thyroglobulin in 14 (73%) of 19 measurements. In 3 (16%) of 19 measurements, thyrotropin receptor messenger RNA was the only blood test useful for disease assessment because of elevated antithyroglobulin antibodies. Overall, to predict thyroid cancer, thyrotropin receptor messenger RNA demonstrated 73% sensitivity, 82% specificity, 62% positive predictive value, 88% negative predictive value, and 79% accuracy.ConclusionThyrotropin receptor messenger RNA provides complementary evaluation to thyroglobulin and fine-needle aspiration for pediatric thyroid nodule management.     

Manserin as a novel histochemical neuroendocrine marker in prostate cancer

ObjectivesTo investigate the presence of manserin in human prostate cancers and to correlate manserin expression with pathologic outcomes and progression-free survival.MethodsEighty-seven patients with recent prostate cancer were classified into 4 groups based on Gleason score, and manserin immunohistochemistry was correlated with Gleason sum grade. To investigate the validity of manserin as a prognostic factor, the Cox proportional hazards regression model was performed on 48 patients in our cohort with T3 or T4 prostate cancer who were initially treated with androgen deprivation therapy.ResultsThe manserin-positive rates of patients with Gleason sums of 6, 7, 8, and ≥9 were 0%, 20.0%, 35.0%, and 48.1%, respectively. Manserin-positive rates were positively correlated with Gleason sums (P = 0.0001). Median times to cancer progression in groups with (n = 8) and without (n = 40) manserin expression were 8 months and 28 months, respectively (P = 0.01). Univariate Cox analysis revealed that manserin expression, clinical stage T4, and high Gleason sum were significantly associated with progression. Multivariate analysis revealed that only 2 factors, manserin expression (hazard ratio (HR) 4.99, P = 0.01) and clinical stage T4 (HR 4.77, P = 0.03), were independent risk factors for progression.ConclusionsThis is the first report of manserin expression in human prostate cancers. Manserin may serve as a marker of prostate cancer progression.     

Prostate cancer antigen-1 as a potential novel marker for prostate cancer

Aim： To examine the expression of prostate cancer antigen-1 （PCA-1） in prostate cancer （PCa） and to validate it as a potential marker for diagnosis of PCa. Methods： In situ hybridization analysis of PCA-1 mRNA expression was performed on 40 benign prostate hyperplasia （BPH）, 16 high-grade prostatic intraepithelial neoplasm （HG-PIN）, 74 PCa and 34 other malignant carcinoma specimens. The level of PCA- 1 expression was semiquanfitatively scored by assessing both the percentage and intensity of PCA- 1 positive staining cells in the specimens. We then compared the PCA-1 expression between BPH, HG-PIN and PCa and evaluated the correlation of PCA-1 expression level with clinical parameters of PCa. Results： PCA-1 mRNA was expressed in the majority of both PCa and HG-PIN specimens but not in BPH and other malignant carcinoma. The expression level of PCA-1 increased along with a high Gleason score （P 〈 0.05）, and was unrelated to other clinical parameters of PCa （all P 〉 0.05）. Conclusion： The data suggest that PCA-1 might be a novel diagnostic marker for PCa, and that increased PCA-1 expression might denote more aggressive variants of PCa.     

血清骨保护素诊断前列腺癌骨转移的初步研究

目的探讨骨保护素（OPG）对前列腺癌骨转移的诊断意义。方法健康男性和前列腺增生患者各30例;对前列腺癌66例患者,分为无骨转移组（M0）36例（局限性前列腺癌30例、淋巴结转移6例）和骨转移组（M1）30例,采用ELISA法测定血清OPG浓度,结合临床资料进行统计学分析。结果M,组血清OPG浓度明显高于其他各组,差异有统计学意义（P〈0．001）。血清OPG与前列腺特异性抗原和碱性磷酸酶浓度呈正相关（r=0．427,0．277;P〈0．001）;与Gleason评分和病理分级呈正相关（r=0．331,0．344;P=0．001）。受试者工作特征（ROC）曲线分析可见,OPG的曲线下面积（AUC）较碱性磷酸酶大,对骨转移的诊断价值高。结论血清OPG对前列腺癌骨转移具有重要诊断价值。     

Focal adhesion kinase as a marker of invasive potential in differentiated human thyroid cancer

Background: The FAK gene encodes a 125-kDa tyrosine kinase (p125^FAK) involved in signal transduction pathways used in cell adhesion, motility, and anchorage-independent growth. Because thyroid carcinomas have a wide variability in their propensity for invasion and metastasis, we studied the expression of FAK in a variety of thyroid tissues. Methods: We synthesized a recombinant N-terminal fragment of the human FAK protein and developed a specific polyclonal antisera. Using Western blot analysis, we assessed the levels of p125^FAK expression in 30 human thyroid tissue samples from 27 patients that included paired normal and malignant specimens. Levels of FAK protein in individual tumors were quantitated by densitometric scanning of the immunoblots, and the results were correlated with tumor histology and biologic behavior. Results: The levels of FAK expression were directly correlated with thyroid carcinomas demonstrating the most aggressive phenotypes. The highest levels of p125^FAK were seen in follicular carcinomas and tumors associated with distant metastatic foci. In contrast, neoplastic thyroid tissues with limited invasive potential, such as papillary carcinomas, follicular adenomas, and other nonmalignant thyroid lesions, showed minimal p125^FAK expression. Conclusions: Overexpression of FAK may be part of a mechanism for invasion and metastasis of thyroid cancer. Furthermore, the levels of p125^FAK may serve as a marker of biologic behavior in this disease. Presented at the 48th Annual Cancer Symposium of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

The androgen receptor as a surrogate marker for molecular apocrine breast cancer subtyping

The Androgen Receptor (AR) is a potential prognostic marker and therapeutic target in breast cancer. We evaluated AR protein expression in high-risk breast cancer treated in the adjuvant setting. Tumors were subtyped into luminal (ER+/PgR±/AR±), molecular apocrine (MAC, [ER−/PgR−/AR+]) and hormone receptor negative carcinomas (HR-negative, [ER−/PgR−/AR−]). Subtyping was evaluated with respect to prognosis and to taxane therapy. High histologic grade (p < 0.001) and increased proliferation (p = 0.001) more often appeared in MAC and HR-negative than in luminal tumors. Patients with MAC had outcome comparable to the luminal group, while patients with HR-negative disease had increased risk for relapse and death. MAC outcome was favorable upon taxane-containing treatment; this remained significant upon multivariate analysis for overall survival (HR 0.31, 95%CI 0.13–0.74, interaction p = 0.035) and as a trend for time to relapse (p = 0.15). In conclusion, AR-related subtyping of breast cancer may be prognostic and serve for selecting optimal treatment combinations.     

Apolipoprotein-D: a novel cellular marker for HGPIN and prostate cancer

BACKGROUND: High grade prostatic intraepithelial neoplasia (HGPIN) is a putative pre-malignant lesion of the prostate. While apolipoprotein-D (Apo-D), an androgen-regulated hydrophobic transporter protein, is expressed in prostate tumors, its expression in HGPIN is unknown. METHODS: Immunoreactivity for Apo-D and another androgen-regulated protein, prostate specific antigen (PSA), was investigated in 64 radical prostatectomy tissues by video image analysis. RESULTS: Eighty two percent of prostatectomy specimens demonstrated moderate to strong Apo-D immunoreactivity in areas of HGPIN. In comparison, weak Apo-D immunoreactivity was observed in non-malignant areas in only 24% of specimens. The median (range) percentage cellular area of HGPIN immunopositive for Apo-D (9.7%, 0-42.9), and the cellular concentration of Apo-D (MIOD 3.1, 0-13.3), were intermediate between that of normal (area 0%, 0-53.5%, MIOD 0, 0-12.6) and early stage prostate cancer tissues (area 29.2%, 0-90.8%, MIOD 6.7, 0-28.1). This increase in Apo-D expression from non-malignant, through HGPIN to prostate cancer was statistically significant (P < 0.001), and contrasted with the decrease observed in PSA staining between adjacent areas of normal glands, HGPIN, and cancer (P = 0.026). CONCLUSIONS: The presence of high levels of immunoreactive Apo-D in HGPIN and prostate cancer, but not in non-malignant epithelial cells, is consistent with HGPIN being an intermediate lesion in the transition to prostate cancer, and suggests that cellular Apo-D expression is a marker of malignant transformation of the prostate.     

Summary statement: utility of molecular marker testing in thyroid cancer

The use of molecular markers for thyroid cancer diagnosis, prognosis, and surveillance have been an exciting area of study and change. Recent investigative focus on promising new markers will very likely lead to improvements in the diagnostic utility of fine needle aspiration biopsy (FNAB) in predicting malignancy, as well as provide more accurate prognostic information pre- and postoperatively. The 2010 Annual Meeting of the American Association for Endocrine Surgeons featured a symposium dedicated to molecular marker testing in thyroid cancer and its potential clinical applicability.