Significant Immunohistochemical Expression of Human Chorionic Gonadotropin in High-Grade Osteosarcoma is Rare, but May Be Associated with Clinically Elevated Serum Levels

Abstract

Survival rates have plateaued at 70% for osteosarcoma. Proteins ectopically produced by malignant tumors may provide insight into new therapeutic targets. Osteosarcomas secreting human chorionic gonadotropin (hCG) have been suggested to have a worse prognosis. We examined the frequency of expression of β-subunit of hCG (β-hCG) in pretreatment osteosarcoma biopsies, and asked if it was associated with various clinical prognostic parameters, and the development of metastases. We subjected 51 pretreatment biopsies of high-grade osteosarcoma, from 51 patients, to β-hCG immunohistochemistry. In 19 of these patients, postchemotherapy metastatic biopsies also were examined for β-hCG expression. Clinical information (patient age, sex, survival status, and serum hCG in females only), and tumor characteristics (site, size, and presence of metastases) were recorded. The β-hCG positive and negative biopsies were separated and compared. Of 49 interpretable pretreatment biopsies, 28 (57%) showed positive cytoplasmic β-hCG expression: 27 with sparse positivity (1% of tumor cells) and 1 with frequent positivity (10% of tumor cells). The patient with frequent β-hCG positivity in her pretreatment biopsy had elevated serum hCG (88.2 mIU/mL) at diagnosis, decreasing to undetectable following chemotherapy and definitive resection. There was no difference in clinical parameters or rate of metastasis between β-hCG positive versus negative groups. Expression of β-hCG may be seen in high-grade osteosarcoma, but frequent β-hCG immunohistochemical expression by tumor cells, associated with clinically elevated serum β-hCG, is rare. Recognition that some nongerm cell tumors may produce β-hCG can prevent confusion with malignancies containing neoplastic syncytiotrophoblast cells, including germ cell and trophoblastic tumors.

Uterine malignant leiomyosarcoma associated with high levels of serum beta‐human chorionic gonadotropin: A case report

“… 6 , 20 This is consistent with our findings as well, given the presence of multiple distant metastases and the loco‐regional extent of the disease. However, there are reported cases and a different case series 22 where β‐hCG production was not associated with advanced disease and conclude that it is not a predictor of the sarcoma's biological behavior. 8 , 23 With regard to uterine leiomyosarcomas that secrete β‐hCG, all three cases developed distant metastases; thus, the association with a more adverse outcome is consistent, but as mentioned above, just empirical.…”

Dedifferentiated Liposarcoma With Rhabdomyosarcomatous Differentiation Producing HCG: A Case Report of a Diagnostic Pitfall

“…A significant number of specimens (27 of 51 tumors in one study and 4 of 32 in the other) exhibited weak cytoplasmic HCG expression, and one specimen in each study was strongly positive for HCG. 28,32 This suggested that osteosarcoma may have higher incidence of subclinical HCG expression than previously suspected. Only one HCG producing liposarcoma has been reported in the literature; in that case the tumor was a primary retroperitoneal dedifferentiated liposarcoma with leiomyosarcomatous differentiation.…”

“…17 Although HCG production by carcinomas has been shown to be associated with a more aggressive behavior, there is no consensus on whether paraneoplastic HCG production in sarcomas is associated with a more ominous prognosis. 32 In one case report analysis, 6 of the 7 patients with HCG producing sarcomas of various types succumbed to their disease within 1 year of diagnoses; however, their sarcomas were high grade, therefore whether or not it is an independent prognostic factor remains unclear. 1…”

Don’t cancel the surgery just yet! A case report of positive preoperative pregnancy test due to a soft tissue sarcoma production of ectopic beta human chorionic gonadotropin

“…They also found that all samples with positive staining showed poor histological response to neoadjuvant chemotherapy. Lee et al 9 in 2014 performed a larger study and found that, in 49 pretreated osteosarcoma samples, 57% showed positive β-hCG expression. The group found no clinical difference between the tumors that stained positive and negative for the hormone.…”