Elsevier

Gynecologic Oncology

Volume 93, Issue 1, April 2004, Pages 107-111
Gynecologic Oncology

Detection of pelvic lymph node micrometastasis in stage IA2–IB2 cervical cancer by immunohistochemical analysis

https://doi.org/10.1016/j.ygyno.2003.11.033Get rights and content

Abstract

Objective. The objectives of this study were to (1) determine the incidence of lymph node micrometastasis in cervical cancer by immunohistochemical analysis and (2) determine if the presence of micrometastasis is a poor prognostic feature in early cervical cancer.

Methods. We retrospectively reviewed the medical records of 62 patients who underwent radical hysterectomy and lymphadenectomy for FIGO stage IA2–IB2 cervical cancer at Stanford University Hospital from 1990 to 2000. Forty-nine patients with negative lymph nodes were identified. A total of 976 formalin-fixed paraffin-embedded pelvic lymphadenectomy specimens were serially sectioned and stained with anti-cytokeratin antibodies AE1 and AE1/CAM5.2.

Results. Six patients had stage IA2 disease, 37 had stage IB1, and 6 had IB2. The mean age of the patients was 44 years (range, 24–76). Seventy-one percent had squamous cell carcinomas, 22% had adenocarcinomas, and 6% had other types. Lymph node micrometastases were immunohistochemically detected in 4 of the 49 (8.1%) patients, comprising 4 of 976 (0.41%) pelvic lymph nodes examined. Twelve of 45 (15.6%) patients with negative nodes had lymph-vascular space invasion (LVSI) whereas 3 of 4 (75%) patients with micrometastases had LVSI. At a mean follow-up time of 39.4 months, 2 of 4 (50%) patients with micrometastasis had recurrent disease, while 3 of 45 (6.7%) patients without micrometastasis developed recurrent disease.

Conclusions. These preliminary data suggest that immunohistochemical detection of pelvic lymph nodes is more frequent in patients with LVSI and may identify patients needing adjuvant chemoradiation.

Introduction

An estimated 12,200 women will be diagnosed with cervical cancer in 2003, and 4100 women will die of this disease [1]. Eighty percent of patients with invasive cervical carcinoma present with early stage disease (FIGO stage IA2–IB1); these patients are usually treated surgically with radical hysterectomy and pelvic lymphadenectomy and the overall survival rate is on the order of 80–90% [2]. Outcome is associated with a variety of prognostic factors, including size of the primary tumor, depth of stromal invasion, presence or absence of lymphatic space invasion, proximity to vaginal margins, and histological type.

The single most important prognostic factor for patients with low stage disease is the presence of lymph node metastases. For patients with stage IB disease, Delgado et al. [3] found a disease-free survival of 85.6% at 3 years for patients with negative pelvic lymph nodes versus 74.4% for patients with one or more positive lymph nodes. The incidence of pelvic lymph node metastases ranges from 8.5% to 21.4% for early stage disease (the incidence of paraaortic lymph node metastases ranges from 5% to 10% in stages IB and IIa disease), but the incidence and implications of lymph node micrometastasis are largely undetermined [2], [4].

Advances in the treatment of cervical cancer have focused on the incorporation of chemotherapy as a radiation sensitizer, and combination chemoradiation has been shown to improve survival and decrease the incidence of distant recurrence in patients with poor prognostic features [5], [6], [7]. Since patients with high-risk factors have been found to benefit from postoperative adjuvant treatment, the presence of pelvic lymph node micrometastases could theoretically play an important role in directing adjuvant therapy in patients with early stage disease in absence of other poor prognostic features [8].

Current methods of detecting lymph node metastasis in cervical cancer are limited to routine histopathological analysis. Although immunohistochemical analysis is currently used for the detection of breast cancer micrometastasis in sentinel lymph nodes and this procedure is being actively investigated in staging procedures for cervical cancer, the incidence and significance of micrometastases detected by immunohistochemical methods in cervical cancer are unknown. In order to address these issues, we examined the pelvic lymph nodes in lymphadenectomy specimens using immunohistological markers for cytokeratin and correlated these findings with other risk factors and outcome.

Section snippets

Patients

Patients who underwent a radical hysterectomy and lymphadenectomy for stage IA2, IB1, and IB2 cervical cancer were identified by a retrospective computerized search of the pathology archived database at Stanford University from 1990 to 2000. Institutional review board approval was obtained for this study. All patients with FIGO stage IA2–IB2 were included (staging was based on International Federation of Gynecology and Obstetrics [FIGO] guidelines). Only patients whose preliminary biopsy or

Results

We retrospectively reviewed the medical records of 62 patients who underwent radical hysterectomy and lymphadenectomy for FIGO stage IA2–IB2 cervical cancer at Stanford University Hospital from 1990 to 2000 under an IRB approved protocol. A total of 49 patients with stage IA2–IB2 cervical cancer who underwent radical hysterectomy and lymphadenectomy with histologically negative lymph nodes were identified. Clinicopathologic characteristics of these patients are shown in Table 1. The mean age of

Discussion

In studies of other cancers, particularly breast cancer, routine histological examination has been found to underestimate the incidence of lymph node metastasis. Historically, it has been reported that serial sectioning of axillary lymph nodes reveals undetected metastases in 7–33% of breast cancer patients [10], [11], [12], [13]. Recently, attention has been turned to enhanced histopathological analysis using techniques such as reverse transcriptase PCR, flow cytometry, and immunohistochemical

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Presented at the 31st Annual Meeting of the Western Association of Gynecologic Oncologists (WAGO), Newport Beach, CA, June 12–15, 2002.

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