Response to letter "DNA micro- arrays will be instrumental in the future diagnosis of cervical dysplasia and neoplasia", by P. K. Wright (doi:10.1093/annonc/mdi109)

E. Barranger*, A. Cortez, F. Commo, O. Marpeau, S. Uzan, E. Darai and P. Callard

Gynecology Department, Hopital TENON4 rue de la Chine, France

* Email: emmanuel.barranger{at}tnn.ap-hop-paris.fr

We want to thank Paul Wright for his comments. Cervical cancer is one of the leading causes of female death due to cancer world-wide. Lymph node status remains the most important prognostic factor. Pelvic lymph node dissection is therefore crucial in therapeutic decision making. Recent advances in therapeutic modalities involving surgery, radiation or chemotherapy have reduced overall cancer death rates, but treatment failure remains relatively high in locally advanced cervical cancer [1Go]. The major cause of failure in treating cervical cancer is probably inability to identify ‘occult’ metastatic lesions. Indeed, despite favourable prognostic features, pelvic recurrence occurs in about 10% of patients with histologically normal pelvic lymph nodes and clear surgical margins around the primary tumour [2Go]. Occult metastases in the lymphatic system probably account for disease recurrence as has been demonstrated in endometrial cancer by Yabushita et al. [3Go]. The sentinel node (SN) procedure has emerged as an alternative to systematic lymphadenectomy, reducing treatment-related morbidity without compromising patient survival. Another potential advantage is the thorough nature of SN analysis, with immunohistochemical (IHC) staining of multiple sections; this may facilitate the detection of occult metastases (such micrometastases could explain some pelvic recurrences in women with negative standard histologic findings). There are several methods to evaluate SN for occult metastatic tumour cells, including conventional histopathological evaluation (H&E), immunohistochemical staining of multiple sections and molecular biological techniques (RT–PCR). Recently, DNA microarrays have been shown to predict axillary lymph node metastasis in breast cancer [4Go]. This technique is probably superior to H&E and IHC to identify occult SN metastasis. Finally, DNA microarrays in cervical cancer might contribute to predicting the development of distant metastasis (i.e. recurrence). However, this approach is slightly more costly and laborious than IHC and H&E. Further studies will be needed to compare the accuracy of conventional histological analysis (i.e. H&E and IHC) of SN with DNA microarrays to detect occult metastasis in patients with cervical cancer.


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1. Green JA, Kirwan JM, Tierney JF et al. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet 2001; 358: 781–786.[CrossRef][ISI][Medline]

2. Inoue T, Morita K. The prognostic significance of number of positive nodes in cervical carcinoma stages IB, IIA, and IIB. Cancer 1990; 65: 1923–1927.[ISI][Medline]

3. Yabushita H, Shimazu M, Yamada H et al. Occult lymph node metastases detected by cytokeratin immunohistochemistry predict recurrence in node-negative endometrial cancer. Gynecol Oncol 2001; 80: 139–144.[CrossRef][ISI][Medline]

4. Huang E, Cheng SH, Dressman H et al. Gene expression predictors of breast cancer outcomes. Lancet 2003; 361: 1590–1596.[CrossRef][ISI][Medline]





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