European Journal of Cardiovascular Medicine

Ovarian cancer ranks as the third most common gynecological cancer in India, following cervical and uterine cancers. Despite its relatively lower incidence compared to breast cancer, its mortality-to-incidence ratio is among the highest due to challenges in early detection. Ovarian cancer is often termed the "silent killer" because symptoms are nonspecific and appear only in advanced stages. The heterogeneity of the disease, encompassing diverse histopathological subtypes and genetic mutations, complicates diagnosis and treatment further.

In India, socio-economic disparities, lack of awareness, and limited access to healthcare exacerbate the challenges of early diagnosis. Most women present with advanced-stage disease, which significantly limits treatment options and worsens prognosis. This study investigates the clinicopathological profile of ovarian cancer in Indian women, comparing it with global trends to identify unique regional characteristics and address gaps in care.

Study Design and Setting

This retrospective observational study was conducted at a tertiary care hospital in India, serving as a referral center for gynecological cancers in the region. Ethical approval was obtained from the institutional review board.

Study Population

All cases of primary ovarian cancer diagnosed between January 2013 and December 2022 were included. Inclusion and exclusion criteria were as follows:

Inclusion Criteria:

• Histopathologically confirmed primary ovarian cancer.
• Complete medical records, including clinical, imaging, and pathological data.

Exclusion Criteria:

• Secondary ovarian tumors or metastatic cancers involving the ovary.
• Patients with incomplete records or loss to follow-up before treatment initiation.

Data Collection

Patient records were reviewed to collect data on:

• Demographics: Age, menopausal status, and socio-economic background.
• Clinical Presentation: Symptoms at presentation and duration.
• Tumor Characteristics: Histopathological subtype, tumor grade, and FIGO stage.
• Tumor Markers: CA-125 levels and imaging findings

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Treatment Modalities: Surgery, chemotherapy, and outcomes.

STATISTICAL ANALYSIS

Data were analyzed using SPSS v26. Descriptive statistics summarized demographic and clinical variables. Chi-square tests assessed categorical variables, and Kaplan-Meier curves estimated survival outcomes. A comparative analysis with recent studies was performed to contextualize findings.

Patient Demographics

The study included 456 women diagnosed with ovarian cancer. The mean age at diagnosis was 54.2 years (SD ± 10.8), with the youngest patient aged 22 and the oldest 84 years. A significant proportion of patients (70.6%) were postmenopausal.

Table 1: Demographic Characteristics

Clinical Presentation

Abdominal distension was the most common presenting symptom (62%), followed by pelvic pain (48%) and gastrointestinal complaints (25%). Symptoms were often nonspecific, leading to delays in diagnosis.

Table 2: Clinical Presentation and Duration of Symptoms

Tumor Characteristics

Histopathological analysis revealed that serous carcinoma was the predominant subtype (64%), followed by mucinous carcinoma (12%). Advanced-stage disease (FIGO III/IV) was noted in 78% of cases, reflecting delayed diagnosis.

Table 3: Tumor Characteristics

Elevated CA-125 levels (>35 U/mL) were observed in 392 patients (86%), with a median CA-125 level of 542 U/mL in advanced stages compared to 154 U/mL in early-stage disease.

Treatment and Outcomes

Among the 456 patients, 68% underwent cytoreductive surgery, with optimal cytoreduction (residual tumor<1 cm) achieved in 68% of cases. Neoadjuvant chemotherapy was administered to 43% of patients.

Progression-free survival (PFS) was significantly influenced by the stage at diagnosis and tumor grade. Patients with early-stage disease had a median PFS of 32 months, compared to 15 months for advanced-stage disease.

Table 4: Treatment Modalities and Outcomes

Histopathological Analysis

Histopathology plays a crucial role in the diagnosis and classification of ovarian cancer. Each subtype exhibits distinct microscopic features that aid in prognosis and treatment planning. In this study, the most common subtypes observed were:

1. Serous Carcinoma (64%)

• Gross Appearance: Typically cystic with solid areas. Papillary projections are common.
• Microscopic Features: High-grade serous carcinoma shows pleomorphic nuclei, mitotic figures, and slit-like glandular spaces. Psammoma bodies (calcifications) are often present.
• Immunohistochemistry (IHC): Positive for p53, WT1, and CA-125.

2. Mucinous Carcinoma (12%)

• Gross Appearance: Large, multiloculated cysts filled with mucinous material.
• Microscopic Features: Tall columnar epithelial cells with abundant intracellular mucin. Clear stromal invasion distinguishes it from borderline mucinous tumors.
• IHC: Positive for CK7 and CK20, but negative for WT1.

3. Endometrioid Carcinoma (9%)

• Gross Appearance: Solid and cystic, resembling endometrial tissue.
• Microscopic Features: Glandular structures resembling endometrial adenocarcinoma. Squamous differentiation is common.
• IHC: Positive for estrogen receptor (ER), progesterone receptor (PR), and PAX8.

4. Clear Cell Carcinoma (6%)

• Gross Appearance: Solid or cystic with a yellowish cut surface.
• Microscopic Features: Clear cytoplasm, hobnail cells, and high nuclear grade. Often associated with endometriosis.
• IHC: Positive for Napsin A, HNF-1β, and CK7.

5. Other Subtypes (9%)

• This group includes rarer types such as Brenner tumors, small cell carcinoma, and undifferentiated carcinoma, each with unique microscopic and immunohistochemical characteristics.

Techniques Used for Analysis

1. Hematoxylin and Eosin (H&E) Staining:
• Standard stain used for observing cellular and stromal architecture.
• Highlights nuclear and cytoplasmic details essential for subtype identification.
2. Immunohistochemistry (IHC):
• Performed to confirm the diagnosis and differentiate between subtypes.
• Biomarkers such as WT1, p53, and CA-125 help in classifying ovarian tumors.
3. Special Stains:
• Mucin stains (e.g., PAS or Alcian Blue) for mucinous carcinoma.
• Periodic Acid-Schiff (PAS) for glycogen in clear cell carcinoma.

Findings

1. High-Grade Serous Carcinoma

• Features: Papillary structures lined by cells with marked nuclear atypia and mitotic activity. Psammoma bodies are often seen.
• Microscopic Description: Complex glandular or papillary architecture with nuclear pleomorphism and slit-like spaces.

2. Mucinous Carcinoma

• Features: Large cystic spaces lined by mucin-producing epithelial cells. Invasive foci in the stroma confirm malignancy.
• Microscopic Description: Columnar cells with basal nuclei, abundant cytoplasmic mucin, and occasional goblet cells.

3. Endometrioid Carcinoma

• Features: Tubular and glandular structures resembling endometrial carcinoma, sometimes with squamous differentiation.
• Microscopic Description: Back-to-back glandular proliferation with minimal stroma.

4. Clear Cell Carcinoma

• Features: Large polygonal cells with clear cytoplasm arranged in sheets or tubules. Hobnail cells are characteristic.
• Microscopic Description: Prominent nuclei with clear or eosinophilic cytoplasm.

Key Findings

This study highlights the predominance of advanced-stage ovarian cancer in Indian women, a pattern consistent with other low- and middle-income countries. The mean age of diagnosis is comparable to other Asian populations but slightly younger than Western cohorts.

Histological Variations

Serous carcinoma emerged as the most common subtype, aligning with global trends. However, the relatively higher prevalence of mucinous carcinoma in this cohort could suggest regional or genetic predispositions.

Stage at Presentation

The advanced-stage presentation in 78% of cases underscores the challenges in early diagnosis. Late presentation is likely due to vague symptoms, lack of awareness, and limited access to healthcare in rural areas.

Comparison with Global Studies

• A study from the United States reported 50% early-stage diagnoses, emphasizing the role of screening and healthcare access.
• In contrast, Chinese studies show a similar pattern of late-stage presentation but with a lower prevalence of mucinous carcinoma.

Survival Outcomes

The median PFS of 18 months is lower than that reported in Western studies, reflecting delayed diagnosis and limited treatment options. Access to newer therapies like PARP inhibitors remains restricted in resource-limited settings.

Clinical and Policy Implications

• Enhanced awareness programs targeting rural populations are essential.
• Implementation of cost-effective screening strategies, such as transvaginal ultrasound combined with CA-125 testing, could improve early detection rates.
• Establishing regional cancer registries will facilitate better data collection and targeted interventions.

This retrospective study reveals that ovarian cancer in Indian women is characterized by advanced-stage presentation and a predominance of serous carcinoma. Comparative analysis with global data highlights significant differences in histological patterns and stage distribution. Addressing these disparities through early detection strategies and improved access to healthcare is critical to enhancing outcomes.

1. Prat J. Ovarian carcinomas: Five distinct diseases with different origins and behaviors. Virchows Arch. 2012;460(3):237–49.
2. Torre LA, Trabert B, DeSantis CE, et al. Ovarian cancer statistics, 2018. CA Cancer J Clin. 2018;68(4):284–96.
3. Shaikh R, Mandal AK, Dutta S. Clinicopathological profile of ovarian tumors: A retrospective analysis. Indian J PatholMicrobiol. 2020;63(2):220–6.
4. Global Cancer Observatory. International Agency for Research on Cancer. Available from: https://gco.iarc.fr/
5. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020. CA Cancer J Clin. 2021;71(3):209–49.
6. Gupta N, Bisht D, Agrawal M, et al. Retrospective analysis of ovarian tumors in a tertiary care hospital in India. J ObstetGynaecol India. 2017;67(3):184–90.