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      The prognostic significance of micrometastases in node-negative squamous cell carcinoma of the vulva

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          Abstract

          Nodal involvement is one of the most significant prognostic factors in squamous cell carcinoma (SCC) of the vulva. We conducted a retrospective analysis of 31 women with histologically node-negative SCC from a population-based cohort of Grampian women. Median follow-up was 42 months after radical vulvectomy with groin node dissection. In total, 13 women (42%) were found to have micrometastases on immunohistochemistry. The risk of recurrence was almost 20-fold higher in those with micrometastases compared to those without (hazard ratio=19.6 (95% CI 2.3–171).

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

          N N Teng, Basma F. A. Husain, Margrit Juretzka … (2004)
          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. 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. 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. 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.
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            Molecular quantification and mapping of lymph-node micrometastases in cervical cancer.

            V Gyselman, Alex Shepherd, S Dorudi … (2001)
            A proportion of patients with cancer and lymph nodes negative on histology will develop recurrence. Reverse-transcriptase PCR (RT-PCR) is a highly sensitive method for detection of lymph-node micrometastases, but accurate quantitative assessment has been difficult. We studied primary tumours and 156 lymph nodes from 32 patients with cervical cancer (stage IA2, IB1, and IB2) and 32 lymph nodes from nine patients with benign disease. A fully quantitative, real-time RT-PCR assay was used to document absolute copy numbers of the epithelial marker cytokeratin 19. Primers and probe were designed not to amplify either of the two cytokeratin 19 pseudogenes. All primary tumours and histologically involved lymph nodes (six) had more than 106 copies of cytokeratin 19 mRNA per microg total RNA. Expression of cytokeratin 19 (up to 1.1 x 10(5) copies per microg RNA) was detected in 66 (44%) of 150 histologically uninvolved lymph nodes, and in nodes from 16 of 32 patients with cervical cancer. 15 of these 16 patients with evidence of micrometastases had the highest cytokeratin 19 transcription level in a first lymph-node drainage station (three obturator, six internal, and six external iliac node). Transcription of cytokeratin 19 was found at a low level in just one of 32 lymph nodes obtained from nine patients with benign disease. Median copy number of cytokeratin 19 transcription was significantly higher (>10(3) copies) in association with adverse prognostic features. The results suggest that about 50% of early-stage cervical cancers shed tumour cells to the pelvic lymph nodes. The amount of cytokeratin 19 expression was related to clinicopathological features. Further studies are required to document the clinical implications of molecular micrometastases.
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              Groin recurrence in patients with vulvar cancer with negative nodes on superficial inguinal lymphadenectomy.

              Diane Bodurka, Mary Gordinier, Charles F. Levenback … (2003)
              The objective of this study was to investigate the cause of groin recurrence in patients with vulvar cancer who had negative nodes in their superficial inguinal lymphadenectomy (SIL) specimens. The records of patients with vulvar cancer treated at M. D. Anderson Cancer Center between 1986 and 1997 were reviewed to identify patients with squamous histology, clinical and surgical stage I or II, depth of invasion greater than 1 mm, and primary treatment consisting of radical wide excision and SIL. One hundred four patients met these criteria. Among these, nine experienced recurrent disease that involved one or both of the groins. All of the original hematoxylin and eosin (H&E)-stained slides were reviewed by one pathologist (AM). Then, each paraffin block containing nodal tissue was recut at 40 microm intervals to obtain five sections for H&E staining and two unstained sections to be used for cytokeratin immunostaining if necessary. The median age at diagnosis and primary surgery was 65 years and the median depth of invasion was 4 mm. Seven patients underwent bilateral, and two underwent unilateral, groin dissections. The median number of lymph nodes removed per groin was seven. The median time to recurrence was 22 months. A total of 785 additional H&E-stained slides were prepared and examined at 100x and 400x magnification. No micrometastases were identified, and there were no other suspicious findings. Therefore, immunohistochemical staining was not performed. At recurrence, one patient had a biopsy only, and eight had attempted surgical resection. In two patients, tumor was identified in fibroadipose tissue only; no lymph nodes were identified. Among the other six patients, the median number of lymph nodes resected at the time of the recurrence was five (range 1 to 10). At last report, six patients had died and three were alive and free of disease. Median follow-up for survivors was 63 months (range 42 to 71). These data strongly suggest that groin relapse in patients with negative nodes on SIL is caused by metastatic disease in unresected inguinal nodes. SIL as performed on the patients in this study did not eliminate all sites of nodal metastasis.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Br J Cancer
                Title: British Journal of Cancer
                Publisher: Nature Publishing Group
                ISSN (Print): 0007-0920
                ISSN (Electronic): 1532-1827
                Publication date (Electronic): 18 January 2005
                Publication date Collection: 25 January 2005
                Publication date (Print): 31 January 2005
                Volume: 92
                Issue: 2
                Pages: 222-224
                Affiliations
                [1 ]Gynaecology Oncology Unit, Ward 43, Aberdeen Royal Infirmary, AB25 2ZN, UK
                [2 ]Department of Pathology, Aberdeen Royal Infirmary, AB25 2ZN, UK
                [3 ]Department of Epidemiology, University of Aberdeen, AB25 2ZN, UK
                Author notes
                [* ]Author for correspondence: gnarayansingh@ 123456nhs.net
                Article
                Publisher Item ID: 6602343
                DOI: 10.1038/sj.bjc.6602343
                PMC ID: 2361832
                PubMed ID: 15655537
                SO-VID: e2c8b934-162f-4260-be79-5fbbd20c23e2
                Copyright © Copyright 2005, Cancer Research UK
                History
                Date received : 07 September 2004
                Date revision received : 22 November 2004
                Date accepted : 23 November 2004
                Categories
                Subject: Clinical Studies

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: groin nodes,vulval cancer,micrometastases
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: groin nodes, vulval cancer, micrometastases

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