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Lymphovascular Space Involvement in Cervical Cancer: An Independent Risk Factor
GYNECOLOGIC ONCOLOGY ARTICLE NO.
68, 219 (1998)
GO984980
EDITORIAL Lymphovascular Space Involvement in Cervical Cancer: An Independent Risk Factor Gregorio Delgado, M.D. Department of Obstetrics and Gynecology, Loyola University Medical Center, 2160 South First Avenue, Maywood, Illinois 60153
When lymphovascular spaces (LVS) are unequivocally defined with endothelial lining cells and viable tumors inside the histological structure within the cervix of a patient with an invasive cervical cancer, they are an independent risk factor in prognosis and survival of invasive cervical carcinoma [1]. In a multiinstitutional study of Stage IB cervical cancer treated by radical hysterectomies, only three independent risk factors were identified in relation to disease-free survival: the depth of the invasion, the size of the tumor, and lymphovascular space involvement [1]. Of the 542 patients entered in this study, 276 patients had positive lymphovascular space involvement. Disease-free interval was 77% in the patient with positive LVS versus 88.9% where LVS were negative. In addition, there was a significant correlation between capillary LVS involvement with metastatic pelvic lymph nodes. Twenty-five percent of patients with positive LVS had metastatic lymph nodes versus only 8% when the spaces were negative. The study of Roman et al. [2] brings this concept even further. It quantifies the lymphovascular space by percentage of cervical histopathological sections containing LVS, percentage of sections with tumor containing LVS, the total number of LVS, and maximum number of LVS in high-power fields. These measures of LVS were correlated with the risk of nodal metastasis, concluding that quantity of LVS, as defined by the percentage of all cervical histopathological sections containing LVS, correlates significantly with the risk of lymph node metastasis in women with early stage invasive cervical cancer. Although the study included only 73 patients with cervical cancer, 23 of whom had pelvic node metastasis, it is important information that needs to be expanded. Certainly there are patients with histologic sections where almost all LVS contain metastatic cancer vs other patients’ sections where very few LVS contain cancer cells. Although both patients have positive LVS, the quantity is different; this study confirms that quantity of positive LVS is a better predictor of metastatic lymph nodes. What remains to be seen is whether quantification correlates with survival and disease-free interval. As previously reported, positive LVS is an independent risk factor for diseasefree survival. I believe that this important information will further define the role of positive LVS as a prognostic factor in patients with invasive cervical cancer.
If lymphovascular space involvement is going to be used as a prognostic factor, a strict definition has to be established and it must be unequivocally determined that this indeed has endothelial lining and is a lymphovascular space. When in doubt, this should perhaps be disregarded in some situations, or special stains should be used to further identify the lymphovascular spaces. Special stains have been used to identify endothelial cells lining microvessels, and, highlighted with antifactor VIII related antigen/von Willebrand’s factor (F8RA/VWF), other relatively vessel-specific reagents such as anti-CD31 have proven to be the most sensitive endothelial markers [3]. Immunohistochemical techniques have also been used in the assessment of intratumoral microvessel density as a significant prognostic factor. On the other hand, Tsuruchi et al. [4] compare the use of hemotoxylin and eosin (H&E) staining and immunohistochemical techniques to identify lymphovascular space invasion (LVSI) in endometrial cancer and correlate the presence of LVSI by either technique as an independent prognostic factor. They concluded that the H&E identification of LVSI is an independent prognostic factor; however, LVSI identified by immunohistochemical staining was not. Clearly better histological and immunohistochemical parameters need to be established that can be universally used to standardize the identification of LVSI and recognize it as an important risk factor, not only in cervical cancer, but in other cancers as well. REFERENCES 1. Delgado G, Bundy B, Zaino R, Sevin B, Creasman WT, Major F: Prospective surgical–pathologic study of disease-free interval in patients with stage Ib squamous carcinoma of the cervix: A Gynecologic Oncology Group study. Gynecol Oncol 38:352–357, 1990 2. Roman LD, Felix JC, Muderspach LI, Varkey T, Burnett AF, Qian D, Morrow CP: Influence of quantity of lymphovascular space invasion on the risk of nodal metastases in women with early stage squamous cancer of the cervix. Gynecol Oncol 68:220 –225, 1998 3. Weidner N: Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat 36(2):169 –180, 1995 4. Tsuruchi N, Kaku T, Kamura T, Tsukamoto N, Tsuneyoshi M, Akazawa K, Nakano H: The prognostic significance of lymphovascular space invasion in endometrial cancer when conventional hemotoxylin and eosin staining is compared to immunohistochemical staining. Gynecol Oncol 57(3):307– 312, 1995
219
0090-8258/98 $25.00 Copyright © 1998 by Academic Press All rights of reproduction in any form reserved.
68, 219 (1998)
GO984980
EDITORIAL Lymphovascular Space Involvement in Cervical Cancer: An Independent Risk Factor Gregorio Delgado, M.D. Department of Obstetrics and Gynecology, Loyola University Medical Center, 2160 South First Avenue, Maywood, Illinois 60153
When lymphovascular spaces (LVS) are unequivocally defined with endothelial lining cells and viable tumors inside the histological structure within the cervix of a patient with an invasive cervical cancer, they are an independent risk factor in prognosis and survival of invasive cervical carcinoma [1]. In a multiinstitutional study of Stage IB cervical cancer treated by radical hysterectomies, only three independent risk factors were identified in relation to disease-free survival: the depth of the invasion, the size of the tumor, and lymphovascular space involvement [1]. Of the 542 patients entered in this study, 276 patients had positive lymphovascular space involvement. Disease-free interval was 77% in the patient with positive LVS versus 88.9% where LVS were negative. In addition, there was a significant correlation between capillary LVS involvement with metastatic pelvic lymph nodes. Twenty-five percent of patients with positive LVS had metastatic lymph nodes versus only 8% when the spaces were negative. The study of Roman et al. [2] brings this concept even further. It quantifies the lymphovascular space by percentage of cervical histopathological sections containing LVS, percentage of sections with tumor containing LVS, the total number of LVS, and maximum number of LVS in high-power fields. These measures of LVS were correlated with the risk of nodal metastasis, concluding that quantity of LVS, as defined by the percentage of all cervical histopathological sections containing LVS, correlates significantly with the risk of lymph node metastasis in women with early stage invasive cervical cancer. Although the study included only 73 patients with cervical cancer, 23 of whom had pelvic node metastasis, it is important information that needs to be expanded. Certainly there are patients with histologic sections where almost all LVS contain metastatic cancer vs other patients’ sections where very few LVS contain cancer cells. Although both patients have positive LVS, the quantity is different; this study confirms that quantity of positive LVS is a better predictor of metastatic lymph nodes. What remains to be seen is whether quantification correlates with survival and disease-free interval. As previously reported, positive LVS is an independent risk factor for diseasefree survival. I believe that this important information will further define the role of positive LVS as a prognostic factor in patients with invasive cervical cancer.
If lymphovascular space involvement is going to be used as a prognostic factor, a strict definition has to be established and it must be unequivocally determined that this indeed has endothelial lining and is a lymphovascular space. When in doubt, this should perhaps be disregarded in some situations, or special stains should be used to further identify the lymphovascular spaces. Special stains have been used to identify endothelial cells lining microvessels, and, highlighted with antifactor VIII related antigen/von Willebrand’s factor (F8RA/VWF), other relatively vessel-specific reagents such as anti-CD31 have proven to be the most sensitive endothelial markers [3]. Immunohistochemical techniques have also been used in the assessment of intratumoral microvessel density as a significant prognostic factor. On the other hand, Tsuruchi et al. [4] compare the use of hemotoxylin and eosin (H&E) staining and immunohistochemical techniques to identify lymphovascular space invasion (LVSI) in endometrial cancer and correlate the presence of LVSI by either technique as an independent prognostic factor. They concluded that the H&E identification of LVSI is an independent prognostic factor; however, LVSI identified by immunohistochemical staining was not. Clearly better histological and immunohistochemical parameters need to be established that can be universally used to standardize the identification of LVSI and recognize it as an important risk factor, not only in cervical cancer, but in other cancers as well. REFERENCES 1. Delgado G, Bundy B, Zaino R, Sevin B, Creasman WT, Major F: Prospective surgical–pathologic study of disease-free interval in patients with stage Ib squamous carcinoma of the cervix: A Gynecologic Oncology Group study. Gynecol Oncol 38:352–357, 1990 2. Roman LD, Felix JC, Muderspach LI, Varkey T, Burnett AF, Qian D, Morrow CP: Influence of quantity of lymphovascular space invasion on the risk of nodal metastases in women with early stage squamous cancer of the cervix. Gynecol Oncol 68:220 –225, 1998 3. Weidner N: Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat 36(2):169 –180, 1995 4. Tsuruchi N, Kaku T, Kamura T, Tsukamoto N, Tsuneyoshi M, Akazawa K, Nakano H: The prognostic significance of lymphovascular space invasion in endometrial cancer when conventional hemotoxylin and eosin staining is compared to immunohistochemical staining. Gynecol Oncol 57(3):307– 312, 1995
219
0090-8258/98 $25.00 Copyright © 1998 by Academic Press All rights of reproduction in any form reserved.