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Medullary Thyroid Cancer in Patients Older than 45-Epidemiologic Trends and Predictors of Survival.

ABSTRACT: Sporadic medullary thyroid cancer (MTC) can occur anytime in life although they tend to present at a later age (?45 years old) when the tumors are more easily discernible or become symptomatic. We aimed to identify the factors affecting the survival in patients ?45 years of age diagnosed with MTC. We analyzed the Surveillance, Epidemiology, and End Results (SEER) registry from 1973-2016 focusing on patients ?45 years of age with MTC as an isolated primary. A total of 2533 patients aged ?45 years with MTC were identified. There has been a statistically significant increase of 1.19% per year in the incidence of MTC for this group of patients. The disease was more common in females and the Caucasian population. Most patients had localized disease on presentation (47.6%). Increasing age and advanced stage of presentation were associated with worse survival with HR 1.05 (p < 0.001) and HR 3.68 (p < 0.001), respectively. Female sex and surgical resection were associated with improved survival with HR 0.74 (p < 0.001) and 0.36 (p < 0.001), respectively. In conclusion, the incidence of MTC in patients ?45 years of age is increasing. Patients should be offered surgical resection at an early stage to improve their outcomes.

SUBMITTER: Gogna S

PROVIDER: S-EPMC7692716 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Medullary Thyroid Cancer in Patients Older than 45-Epidemiologic Trends and Predictors of Survival.

Gogna Shekhar S Goldberg Michael M Samson David D Gachabayov Mahir M Felsenreich Daniel M DM Azim Asad A Dong Xiang D Eric XDE

Cancers 20201026 11

Sporadic medullary thyroid cancer (MTC) can occur anytime in life although they tend to present at a later age (≥45 years old) when the tumors are more easily discernible or become symptomatic. We aimed to identify the factors affecting the survival in patients ≥45 years of age diagnosed with MTC. We analyzed the Surveillance, Epidemiology, and End Results (SEER) registry from 1973-2016 focusing on patients ≥45 years of age with MTC as an isolated primary. A total of 2533 patients aged ≥45 years ...[more]

PMID: 33114488

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Project description:BackgroundThe retinoblastoma (RB) transcriptional corepressor 1 protein functions to slow cell-cycle progression. Inactivation of RB by reduced expression and/or hyperphosphorylation allow for enhanced progression through the cell cycle. Murine models develop medullary thyroid carcinoma (MTC) after generalized loss of RB. However, RB expression in MTC has only been evaluated in a small number of tumors, with differing results. The objective of this study was to determine whether reduced expression of RB and/or overexpression of hyperphosphorylated RB predict MTC aggressive behavior.MethodsFormalin-fixed, paraffin-embedded primary thyroid tumors and lymph node metastases from MTC patients were evaluated for calcitonin, RB, and phosphorylated RB (pRB) expression by immunohistochemistry. Two expert pathologists evaluated the slides in a blinded manner, and the immunohistochemistry results were compared to disease-specific survival as a primary endpoint.ResultsSeventy-four MTC samples from 56 patients were analyzed in this study, including 51 primary tumors and 23?lymph node metastases. The median follow-up time was 6.75 years after surgery (range 0.64-24.30 years), and the median primary tumor size was 30?mm (range 6-96?mm). Sixty-six percent of cases were classified as stage IV. RB nuclear expression was diffusely present in 88% of primary tumors and 78% of lymph node metastases. Nuclear pRB expression was present in 22% of primary tumors and 22% of lymph node metastases. On univariate analysis, reduced RB (<75% tumor cell staining) trended with lower MTC-specific survival for primary tumor and metastatic nodes (primary tumor hazard ratio?=?3.54 [confidence interval 0.81-15.47], p?=?0.08; and lymph node hazard ratio?=?4.35 [confidence interval 0.87-21.83], p?=?0.05). For primary tumors, multivariable analysis showed that low nuclear RB expression was independently associated with worse disease-specific (p?=?0.01) and overall (p?=?0.02) survival. pRB levels were not associated with survival for either primary tumor or lymph node metastases.ConclusionsReduced RB expression is associated with decreased patient survival in univariate and multivariable analyses, independent from patient age at surgery or advanced TNM stage. Future studies involving larger MTC patient populations are warranted to determine if lower RB expression levels may serve as a biomarker for aggressive disease in patients with MTC.

Project description:Background: Despite advances in targeted kinase inhibitor development for patients with medullary thyroid cancer (MTC), most patients develop resistance and would benefit from alternative approaches. Immune-based therapies are now considered for patients with progressive MTC. This study is the first comprehensive assessment of the immune milieu, immune-suppressive molecules, and potential tumor antigens in patients with MTC. Methods: Primary and/or regionally metastatic tumor tissues from 46 patients with MTC were screened for immune infiltrates by using standard immunohistochemistry (IHC) and further analyzed by multispectral imaging for T cell and myeloid markers. RNASeq expression profiling was performed in parallel. RNASeq, targeted sequencing, and IHC techniques identified cancer-associated mutations and MTC-enriched proteins. Results: Organized immune infiltration was observed in 49% and 90% of primary and metastatic tumors, respectively. CD8+ cells were the dominant T cell subtype in most samples, while CD163+ macrophages were most frequent among myeloid infiltrates. PD-1+ T cells were evident in 24% of patients. Myeloid subsets were largely major histocompatibility complex II (MHCII-), suggesting a dysfunctional phenotype. Expression profiling confirmed enrichment in T cell, macrophage, and inflammatory profiles in a subset of samples. PD-L1 was expressed at low levels in a small subset of patients, while the immune regulatory molecules CD155 and CD47 were broadly expressed. Calcitonin, GRP, HIST1H4E, NOMO3, and NPIPA2 were highly and specifically expressed in MTC. Mutations in tumor suppressors, PTEN and p53, and mismatch repair genes, MSH2 and MSH6, may be relevant to disease progression and antigenicity. Conclusions: This study suggests that MTC is a more immunologically active tumor that has been previously reported. Patients with advanced MTC should be screened for targetable antigens and immune checkpoints to determine their eligibility for current clinical trials. Additional studies are necessary to fully characterize the antigenic potential of MTC and may encourage the development of adoptive T cells therapies for this rare tumor.

Dataset Information

Medullary Thyroid Cancer in Patients Older than 45-Epidemiologic Trends and Predictors of Survival.

Publications

Medullary Thyroid Cancer in Patients Older than 45-Epidemiologic Trends and Predictors of Survival.

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