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Pathology Underrates Colon Cancer Extranodal and Nodal Metastases; Ex vivo Radioimmunodetection Helps Staging

Authors' Affiliations: ¹ Service de Chirurgie Digestive et Générale, Groupe Hospitalier Diaconesses-Croix Saint Simon, Paris, France; ² Université Pierre et Marie Curie-Paris 6, Paris, France; ³ AP-HP Hôpital Saint-Antoine, Service de Médecine Nucléaire, Paris, France; ⁴ AP-HP Hôpital Saint-Louis, Département de Biostatistiques et Informatique Médicale, Paris, France; ⁵ AP-HP Hôpital Saint-Louis, Service de Médecine Nucléaire, Paris, France; ⁶ AP-HP Hôpital Tenon, Service de Médecine Nucléaire Paris, France; ⁷ Institut National de la Sante et de la Recherche Medicale, U339, Paris, France; ⁸ Institut National de la Sante et de la Recherche Medicale, U773, Paris, France; ⁹ Université Denis Diderot-Paris 7, UMR S773, Paris, France; ¹⁰ Centre National de la Recherche Scientifique, GDR 2352, Marseille, France; ¹¹ Institut National de la Sante et de la Recherche Medicale, U601, Nantes, France; and ¹² Université de Nantes, Nantes, France

Requests for reprints: Anne Gruaz-Guyon, Institut National de la Sante et de la Recherche Medicale, U773, CRB3, BP 416, 16 Rue Henri Huchard, Cedex 18, Paris, 75870, France. Phone: 33-144856310; Fax: 33-144856138; E-mail: gruaz{at}bichat.inserm.fr or A. Sézeur, Service de Chirurgie Générale et Digestive, Groupe Hospitalier Diaconesses-Croix Saint Simon, 18 rue du Sergent Bauchat, Paris, 75012, France. Phone: 33-144741174; Fax: 33-144742875; E-mail: asezeur{at}hopital-dcss.org.

Purpose: Colorectal carcinoma is frequently accompanied by small lymph nodes metastases that often escape pathologic examination. We evaluated whether ex vivo radioimmunodetection with the Affinity Enhancement System (AES) could improve detection of mesocolonic metastases.

Experimental Design: A bivalent ¹¹¹In-labeled hapten was injected (16 patients) 4 days after a bispecific antibody (anticarcinoembryonic antigen, antihapten). Surgery was done 1 to 3 days later, and radioactive uptake in the mesocolon was recorded. Extensive pathologic examination of the mesocolon (reference method) was done after fat dissolution. This method visualizes all lymph nodes but is not in routine use.

Results: The reference method disclosed 705 nodes. There was no significant difference between the number of node metastases detected by AES or by the reference method (16 versus 17). Better detection would have been obtained by AES than by routine pathology (P < 0.01). In addition 12 extranodal metastases were found in this study of which eight were detected by AES. The prognostic importance of such extranodal metastases has been underlined in the literature. Routine pathology combined with AES would have disclosed all node metastases and 86% of total metastases versus 35% by routine pathology alone.

Conclusions: Ex vivo radioimmunodetection could improve nodal and extranodal metastases detection in patients with colorectal cancer. Its value for improving pathologic analysis, together with the effect of these small metastases on prognosis, should be further evaluated. The benefit of adjuvant chemotherapy for patients upstaged with radioimmunodection should also be assessed because adjuvant chemotherapy improves the 5-year survival of stage III patients.