Ovarian carcinoma (OC) is the most prevalent gynecologic malignancy. Serous ovarian carcinoma (SOC) is the most common subtype. That is grouped into 2 types based on histologic characteristics (high-grade and low-grade) [1] .

The standard first-line treatment for these tumors is debulking surgery followed by chemotherapy. However, the 5-year survival rate is less than 50% due to local invasion, early metastasis and the first presentation with advanced disease stage [2] .

The outcome in these patients depends on stage at diagnosis, extent of residual disease after surgery and histological subtype [3] .

High grade serous ovarian cancer (HGSC) is considered the most lethal and frequent type of epithelial ovarian cancer (EOC). It has poor long term prognosis due to a combination of factors: late detection, great metastatic potential and resistance to available therapeutic drugs [4] .

Various studies aimed to introduce new biological prognostic markers in ovarian carcinoma. Estrogen receptor promoter methylation can be used to predict overall survival in low grade tumors [5] . However, till today, no reliable biological marker is generally accepted [3] . The improvement of biological prognostic markers is necessary for specification of anti-cancer therapy [6] .

The most clinically valuable ovarian carcinoma biomarker, CA125, has been used to evaluate therapeutic response and check recurrence of EOC. However, it lacks both sensitivity and specificity. Elevated CA125 levels in multiple gynecological conditions decreased its specificity; also, a high proportion of epithelial ovarian cancers do not express CA125 [7] .

Galectins constitute a gene family of widely distributed B-galactoside-binding glycoproteins with high affinity for β-galactoside. It is expressed in many tumor types such as astrocytoma, melanoma, thyroid, colon, bladder, and ovarian cancers [8] .

Galectin-1 is involved in many physiological and pathological process including cell-cell and cell-matrix interactions, cell growth, inflammatory reaction, immune regulation, cell differention and tumor progress [9] .

Several studies suggest that dysregulation of galectin-1 has a link to invasion and metastasis, formation of cancer cells which will promote growth of tumors, angiogenesis and keep the cells away from being destroyed by the immune response of the host [10] .

It was found that galectin-1 is increased in cancer cells as reported in thyroid carcinoma by Chiariotti et al., 1995 [11] and by Xu et al., 1995 [12] . Also, increased galectin-1 expression presented with breast cancer and ovarian cancer [13] .

Gal-1 was detected in neighboring cancer associated fibroblasts and cancer stroma of the primary prostate cancer by Van den Brule et al., 2001 [14] , though Galectin-1 is strongly expressed in ovarian cancer [15] . However, its potential usefulness as a diagnostic or prognostic marker remains unclear.

In this work, we investigated serum level of Galactin-1 and its cellular expression in serous epithelial ovarian cancer in different stages trying to find out its significance as a diagnostic and prognostic marker.

This is a cross sectional study, conducted in Gynecology and Obstetrics, pathology, clinical pathology and clinical oncology departments, Zagazig University Hospitals between March 2016 and April 2019. Ethical approval was granted by Zagazig faculty of Medicine Research and Ethics Committee prior to conducting the study. Full clinical data together with informed consent were obtained from all subjects prior to sample collection.

Surgical assessment was used to decide the clinical stages and metastases presence according to the FIGO classification 2014. Histopathological evaluation was carried out to determine cancer types and the grades.

The study included 95 females that were divided into I-Control group: Twenty five healthy females.

II-Patients group: Seventy females who were diagnosed to have serous ovarian carcinoma (SOC) at different stages: Stage I: 8 cases, Stage II: 12 cases, Stage III: 32 cases and Stage VI: 18 cases. Eighteen cases were low grade, while 52 cases were high grade. We excluded any patient who had previous chemo or radiotherapy and females with benign or borderline tumors.

All patients were followed for up to 3 years after surgery.

Epithelial ovarian cancers (EOC) represent 90% of ovarian cancers which is the most common cause of death from gynecological malignancies and there has been a sustained interest to identify new biomarkers that detect progression and prognosis of EOC [2] .

Continuous variables were expressed as mean (95% CI); categorical variables were expressed as number (percentage); †Log rank test; p < 0.05 is significant.

CA125 is the most clinically useful ovarian cancer biomarker, but it is not secreted by 20% of EOC. Also, it lacks both sensitivity and specificity in early detection, thus identification of more specific and sensitive markers to detect patients at early stages is required [18] .

This need for a new marker is essential because of high rate of recurrence of ECO after treatment [19] . The poor survival rate is due to high grade serous carcinomas and its late diagnosis [20] .

Galectin-1 is a 14-kDa laminin-binding galectin, that may have a role in a variety of physiological and pathological processes as cell-cell and cell matrix interaction, cell growth, inflammatory and immune regulation [21] .

Galectin-1 was detected to accumulate in ovarian cancers. However, its potential as diagnostic and prognostic marker for serous ovarian carcinoma is unclear [15] .

The aim of this study was to evaluate circulating galectin-1 level as well as its expression by immunohistochemical staining in tumor and peri-tumoral stromal cells in SOC trying to find its significance in diagnosis and prognosis of these tumors.

Continuous variables were expressed as mean ± SD & median (range); Categorical variables were expressed as number (percentage); ŸMann Whitney U test; ‡Chi-square test; §Chi-square test for trend; p < 0.05 is significant.

We studied serum level of Gal-1 in 70 patients with SOC at different stages and 25 healthy controls. The mean values of serum Gal-1 were significantly higher in SOC patients than in controls (p < 0.001)

Serum level of Gal-1 was significantly associated with the FIGO stage of SOC (p < 0.001) and higher in stage III, IV compared to stage 1, II. So normal or low Gal-1 level ; may suggest absence of metastasis.

These results are supported by Chen et al., 2015 [17] who reported that serum Gal-1 level was elevated in relation to tumor progression, and they suggested that the increase in serum Gal-1 level is associated with the occurrence of metastasis.

So, we can imply that the metastatic spread of SOC is associated with higher level of circulating Gal-1. This finding may open a view for detection of early spread of SOC.

Serum level of CA125 was significantly raised in patients with SCO compared to controls p < 00.001, a finding that is supported by Hogdal et al., 2007 [22] .

We reported a statistically significant direct correlation between serum Gal-1 level and CA 125 level in SOC, a finding that is supported by Labrie et al., 2017 [6] . On comparing both of them in diagnosis of SOC we found that serum Gal-1 was more accurate than does CA125, as serum Gal-1 was 100% specific, sensitive and accurate in diagnosis of SCO at cut off value of 135 ng/ml with positive and negative predictive values of 100%, while CA 125 at cut off value > 49 u/ml was 88.5% 96 %, 98.4%, 75% and 90.5% in sensitivity, specificity, positive, negative predictive values and accuracy in diagnosis of SOC p < 0.001.

Similar results were obtained by Chen et al., 2015 [17] who found that the association between Gal-1 and CA125 is highly significant, that confirm the lack of independence between these two markers. They found also Gal-1 was more sensitive than CA125 as a false positive obtained by CA125 was negative obtained by Gal-1, and 98% of SOC who are positive by CA 125 were positive by Gal-1.

From these results we can suggest measuring Gal-1 in every patient diagnosed with SOC to simplify decision making before treatment as high serum level suggest metastasis.

After immunohistochemical staining of the 70 cases, we found that strong expression of Gal-1 was detected in tumor cells in 46 patients (65.7%) which was much higher than patients with weak expression (34.3%). We also found strong expression in peri-tumoral stroma in 48 patients (68.6%), a percent which is higher than that with weak expression p < 0.001

High serum level of Gal-1 in SOC patients was associated with strong Gal-1 expression in tumor and stromal cells compared to those with weak expression p < 0.001 and p = 0.002, respectively.

Similar results were obtained for serum level of CA125 and expression of Gal-1 in tumors and peri-tumor stromal cells, the level was higher in Gal-1 strong expression cases compared to weak expression p = 0.001 and p = 0.025 respectively.

After immunohistochemical staining, tumor cell strong expression of Gal-1 was more frequent in patients with advanced stage compared with early stages as it was found in 37.5%, 50%, 68.8% and 83.3% in stage I, II, III, IV respectively.

Strong Gal-1 expression in stromal cells was also more frequent in advanced stages of SOC (25%, 66.7%, 68.8% and 88.9%) in stages I, II, III, IV respectively. Labrie et al., 2017 found strong association between Gal-1 expression and higher FIGO stage of SOC.

Gal-1 showed strong IHC expression both in tumor and peri-tumoral stroma cells in the presence of lymphadenopathy, but did not reach statistically significant level.

High grade SOC were associated with strong Gal-1 expression both in tumor and stromal cells compared to low grade (84.6% vs 11.1%) p < 0.001 and 982.7% vs 27.8%) p < 0.001, respectively.

There was a significantly statistic difference between survivors and non-survivors as regarding Gal-1 expression in peritumoral stromal cells (p = 0.002). Gal-1 expression is associated with poor survival. This was in accordance with Chen et al., 2015 [17] and Labrie et al., 2017 who found that strong Gal-1 expression in tumor cells and stromal cells is associated with poor prognosis. No significant difference was detected between survivors and non-survivors regarding Gal-1 expression in tumor cells p = 0.136, a result supported by Chen et al., 2015 [17] and Labrie et al., 2017 [6] .

High serum level of both Gal-1 and CA125 were significantly associated with poor survival p < 0.001 and p = 0.009 respectively as supported by Labrie et al., 2017 and they stated that high Gal-1 in circulation and its tissue expression in SOC may be useful for follow up patients with SOC.

This poor prognosis of SOC with high expression of Gal-1 in circulation and in peritumoral stromal cells suggests its possible role in favoring metastasis through enhancing spread of tumor cells, promoting their embolization, elevating tumor vascular permeability and conferring a selective support to metastatic cells [23] [24] .

These results that demonstrated the increased Gal-1 in serum and cancer associated stromal cells could be important in cancer progression and poor survival.

After follow up period of 3 years with the mean of 14 months, we found overall survival rate was associated with strong stromal Gal-1 expression p = 0.002, stage of SOC, p = 0.009 and the presence of lymphatic spread p < 0.001.

These results support the usefulness of Gal-1 immunohistochemical expression in peri-tumoral cells as prognostic biomarker for the possibility of successful treatment or the possibility of chemotherapeutic resistance.

These findings were supported by Chen et al., 2015 [17] and Labrie et al., 2017 [6] who found 5-years OS and DFS were associated with strong Gal-1 expression in peri-tumoral stromal cells.

There may be some possible limitations of our study as the limited number of patients included the financial problems and the difficulty of follow up. We recommend a study on large scale.

We can conclude that serum Gal-1 and its tissue level are over-expressed in SOC patients on progression of disease; this may support its usefulness as non-invasive biomarker for diagnosis and prognosis of these patients.

All authors contributed in this research paper and have approved the final article.

There are no funding sources for this research. It was completely paid by the researchers with no external funding sources.

The authors have declared no conflict of interest.

Abdelwahab, M.M., Ebian, H.F., Ibrahim, T.R., Badr, M.S., Lashin, M.E.-B., Yassin, M.A., Ismail, A.M. and Obaya, A.A. (2019) Clinical Significance of Serum Galectin-1 and Its Tissue Immunohistochemical Expression in Serous Ovarian Carcinoma Patien. Open Journal of Obstetrics and Gynecology, 9, 937-953. https://doi.org/10.4236/ojog.2019.97091