The Precursor for Nerve Growth Factor (proNGF) in Thyroid Cancer Lymph Node Metastases: Correlation with Primary Tumour and Pathological Variables

Abstract

Metastases in thyroid cancer are associated with aggressive disease and increased patient morbidity, but the factors driving metastatic progression are unclear. The precursor for nerve growth factor (proNGF) is increased in primary thyroid cancers, but its expression or significance in metastases is not known. In this study, we analysed the expression of proNGF in a retrospective cohort of thyroid cancer lymph node metastases (n = 56), linked with corresponding primary tumours, by automated immunohistochemistry and digital quantification. Potential associations of proNGF immunostaining with clinical and pathological parameters were investigated. ProNGF staining intensity (defined by the median h-score) was significantly higher in lymph node metastases (h-score 94, interquartile range (IQR) 50–147) than in corresponding primary tumours (57, IQR 42–84) (p = 0.002). There was a correlation between proNGF expression in primary tumours and corresponding metastases, where there was a 0.68 (95% CI 0 to 1.2) increase in metastatic tumour h-score for each unit increase in the primary tumour h-score. However, larger tumours (both primary and metastatic) had lower proNGF expression. In a multivariate model, proNGF expression in nodal metastases was negatively correlated with lateral neck disease and being male. In conclusion, ProNGF is expressed in locoregional metastases of thyroid cancer and is higher in lymph node metastases than in primary tumours, but is not associated with high-risk clinical features.

Nerve growth factor and post-infarction cardiac remodeling

“…Дисбаланс NGF/proNGF связан с воспалением и нейродегенерацией [25]. Всё больше данных свидетельствуют о том, что в дополнение к своим нейротрофическим функциям proNGF и NGF участвуют в нескольких биологических процессах, включая иммунный ответ, воспалительный ответ, лёгочную гипертензию, заживление ран и метастазирование рака [45,46,49]. Исследования NGF и его рецепторов обозначили новые терапевтические подходы при злокачественных новообразованиях, диабете, хронических ранах и сердечно-сосудистых заболеваниях.…”

“…NGF не только играет важную роль в поддержании роста симпатических нейритов и повышении активности ферментов, связанных с синтезом катехоламинов, но также является медиатором боли, участвует в ускорении скорости заживления ран и переломов, реализации иммунного и воспалительного ответов, метастазировании рака [45,46,[49][50][51]. По сравнению с синовиальной жидкостью здоровых суставов концентрация NGF выше в синовиальной жидкости суставов со структурными остеоартритическими изменениями (p = 0,032) или острым септическим воспалением (p = 0,006) [50].…”

ProNGF Expression and Targeting in Glioblastoma Multiforme

“…Interestingly, proNGF has been associated with progression and aggressiveness of several malignancies, including breast cancer [ 13 , 14 ], prostate cancer [ 15 ] and melanoma [ 16 ]. In thyroid cancer, proNGF is increased [ 17 ] and proNGF levels are higher in thyroid cancer lymph node metastases than in primary tumors but is not associated with high-risk clinical features [ 18 , 19 ]. While proNGF has previously been reported to be secreted from the GBM cell line U87MG [ 20 ], the expression and potential function of proNGF in patient samples is unclear.…”

Analysis of β-nerve growth factor and its precursor during human pregnancy by immunoaffinity-liquid chromatography tandem mass spectrometry

“…β-Nerve growth factor (NGF) and its precursor proNGF are important neurotrophins that have differing functions. NGF promotes neuronal growth, development and differentiation and is generally neuroprotective 1 , while proNGF has seemingly contradictory functionality 2 , and has been found overexpressed in thyroid cancers compared to normal 3 . Reports published indicate both support for the growth and survival of neurons 4 , 5 , as well as neuronal death 6 , 7 .…”