Abstract
Ovarian cancer (OC) spread to retro-peritoneal lymph nodes is detected in about one out of two patients at primary diagnosis. Whether the histologic pattern of lymph node involvement i.e., intra-(ICG) or extracapsular (ECG) cancer growth may affect patients’ prognosis remains unknown. The aim of the current study was to analyze the prevalence of ECG and ICG in lymph node positive ovarian cancer. We further investigated whether ECG may be related to patients’ prognosis and whether biomarkers expressed in the primary tumor may predict the pattern of lymph node involvement. Lymph node samples stemming from 143 OC patients were examined for presence of ECG. Capsular extravasation was tested for statistical association with clinico-pathological variables. We further tested 27 biomarkers that had been determined in primary tumor tissue for their potential to predict ECG in metastatic lymph nodes. ECG was detected in 35 (24.5%) of 143 lymph node positive patients. High grade (p = 0.043), histologic subtype (p = 0.006) and high lymph node ratio (LNR) (p < 0.001) were positively correlated with presence of ECG. Both ECG (p = 0.024) and high LNR (p = 0.008) were predictive for shortened overall survival. A four-protein signature determined from the primary tumor tissue was associated with presence of concomitant extracapsular spread in lymph nodes of the respective patient. This work found extracapsular spread of lymph node metastasis to be a common feature of lymph node positive ovarian cancer. Since ECG was positively associated with grade, LNR and shortened overall survival, we hypothesize that the presence of ECG may be interpreted as an indicator of tumor aggressiveness.
Highlights
Metastatic spread to lymph nodes is common in solid tumors and is counted as one of the most potent prognostic determinants
We found that expression of Mucin-1, Gal-3nuc, Gal-8nuc, and G‐Protein coupled estrogen (GPER) were statistically associated with capsular extravasation
We introduced a four-marker signature built by VU4H5, GPER, and Gal-3/8 which was predictive for extracapsular growth (ECG) in associated lymph nodes with relatively good sensitivity and specificity
Summary
Metastatic spread to lymph nodes is common in solid tumors and is counted as one of the most potent prognostic determinants. Apart from lymph node involvement per se, the histological growth pattern of neoplastic cells within the lymph node may add further prognostic information [1,2]. The phenomenon of extracapsular growth (ECG), i.e., extension of cancer cell invasion beyond the connective tissue capsule of the lymph node, has been linked to tumor aggressiveness in many cancer entities [1,2,3,4,5,6]. ECG has become an established prognostic factor for gastrointestinal, breast, Cancers 2019, 11, 924; doi:10.3390/cancers11070924 www.mdpi.com/journal/cancers. Regarding squamous cell cancer of the vulva and cancers of the head/neck, ECG has even been incorporated into the official cancer staging systems, respectively [7]
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