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A Preliminary Evaluation of Calcitonin and PDN-21 As Tumor Markers for Lung Cancer

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A Preliminary Evaluation of Calcitonin and PDN-21 As Tumor Markers for Lung Cancer Henry Ford Hospital Medical Journal Volume 37 Number 3 Article 31 9-1989 A Preliminary Evaluation of Calcitonin and PDN-21 as Tumor Markers for Lung Cancer J. J. Body J. C. Dumon J. P. Sculier G. Dabouis H. Lacroix See next page for additional authors Follow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournal Part of the Life Sciences Commons, Medical Specialties Commons, and the Public Health Commons Recommended Citation Body, J. J.; Dumon, J. C.; Sculier, J. P.; Dabouis, G.; Lacroix, H.; Libert, P.; Richez, M.; Bureau, G.; Mommen, P.; Raymakers, N.; Paesmans, M.; and Klastersky, J. (1989) "A Preliminary Evaluation of Calcitonin and PDN-21 as Tumor Markers for Lung Cancer," Henry Ford Hospital Medical Journal : Vol. 37 : No. 3 , 190-193. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol37/iss3/31 This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. A Preliminary Evaluation of Calcitonin and PDN-21 as Tumor Markers for Lung Cancer Authors J. J. Body, J. C. Dumon, J. P. Sculier, G. Dabouis, H. Lacroix, P. Libert, M. Richez, G. Bureau, P. Mommen, N. Raymakers, M. Paesmans, and J. Klastersky This article is available in Henry Ford Hospital Medical Journal: https://scholarlycommons.henryford.com/ hfhmedjournal/vol37/iss3/31 A Preliminary Evaluation of Calcitonin and PDN-21 as TUmor Markers for Lung Cancer J.J. Body,* J.C. Dumon,* J.P. Sculier,* G. Dabouis,* H. Lacroix,* P. Libert,* M. Richez,* G. Bureau,* P. Mommen,* N. Raymakers,* M. Paesmans,* J. Klastersky,* and the EORTC Lung Cancer Working Party* Immunoreactive calcitonin (ICT) can he eclopically secreted by lung cancer cells and has been propo.sed as a tumor marker for bronchial neoplasms. Since PDN-21 (katacalcin or the carboxyl- terminal flanking peptide of the calcitonin gene) and CT are cosecreted in normal subjects and in patients wdh medullary thyroid carcinoma (MTC), we soughl lo delermine the potential ulilily of PDN-21 as a tumor marker for lung cancer We measured carcinoembryonic antigen (CEA), neuron- specific enolase (NSE), iCT. and PDN-21 in 119 lo 378 healthy subjects, 88 to 91 patients wilh benign pulmonary diseases, and 249 patients wilh advanced lung cancer (108 small cell lung cancers and Ml other forms). Tumor marker specificity was satisfaclory: the percentage of increased values (grealer lhan the 95lh percentile of normal subjects) in patients wilh benign pulmonary diseases varied from 9% (NSE, PDN-21) to 12% (CEA). PDN-21 was a more sensdive marker for lung cancer than iCT; the percenlage of increased values was 44% for PDN-21 versus 19% for iCT, and 51% versus 23% for the subgroup of patients wilh small cell lung cancer (SCLC). PDN-21 concentrations were increased in 69 (34%) of202 patients with a normal iCT level, whereas iCT concentrations were increased in only six (4%) of 139 patients with a normal PDN-21 level. However, markedly elevated concentrations oflhe two markers generally occurred in the same patients and the correlation beiween the two markers was significanl (r, = 0.60; P < O.OI). PDN-21 provided complementary information lo that from the classical markers NSE and CEA. PDN-21 was thus elevated in seven (47%) qf 16 patients with SCLC and a normal NSE level, and in 19 (30%) of 63 patients with non-SCLC and a normal CEA level. Immunodilulion curves of sera wilh elevaled concentrations of PDN-21 were slrictly paraUel to the .standard curve, suggesting lhal the assay essentially measured authentic PDN-21. These preliminary results suggest lhal PDN-21 and possibly other CT gene producls are worthwhile in furlher biologic and clinical investigations in lung cancer (Henry Ford Hosp Med J 1989:37:190-3) everal authors have reported increases in circulating cal­ (CEA) and neuron-specific enotase (NSE) (Pharmacia Inc, Up­ S citonin (CT) in various other cancers than medullary thyroid psala, Sweden), iCT (INCStar, Stillwater, MN), and PDN-21 carcinoma (MTC), parricularly in lung cancer (1-3). The se­ (Medgenix Diagnostics, Fleurus, Belgium). The assays' detec­ creted forms are generally larger than monomeric CT (4), and it tion limits were 40 pglmL for iCT and 7 pglmL for PDN-21, and is thus more adequate to speak of immunoreactive CT (iCT). undetectable values were assigned levels of 20 pglmL for iCT The frequency of etevated values varies much between studies and 3.5 pg/mL for PDN-21. but has been higher than 50% in some series of patients with small cell lung cancer (SCLC) (3). Measurement of iCT could Subjects be useful for monitoring the tumor mass in SCIXT (5), but re­ Normal values were detennined in 377 healthy subjects for ported series are small and do not include valid comparisons iCT (251 mates and 126 females; median age 43 years, range 18 with classical tumor markers. PDN-21 (katacalcin or the carboxyt-terminal flanking peptide of the calcitonin gene) derives from the same precursor as CT Submitted for publication: October 24. 1989. and is cosecreted with CT in healthy subjects and in patients Accepted for publication: November 20, 1989. "'Service de Medecine et Laboratoire d'Investigation Chnique H.J. Tagnon. Unite d'En- with MTC (6,7). In our studies of tumor markers for lung cancer docrinologie, Institut Jules Bordet. Universite Libre de Braxelles, Belgium. (8,9), we investigated the possibility that this cosecretion might tParticipating centers include the Institute J. Bordet. Brussels, Belgium: Hopital de War- quignies, lioussu; CHU Nantes, Nantes, France: Group Medical St Remy, Reims, France: be present in other cancers than MTC and that PDN-21 might be Hopital Civil de Charieroi, Charieroi, Belgium: CHU A. Vesale, Montignies-le-Tilleul, a potentially useful tumor marker for lung cancer. Belgium: Hopital Bragmann, Brussels, Belgium; Clinique St Luc, Bouge, Belgium: Hopital de la Madeleine, Ath, Belgium: IMC Mutualites Socialistes, Toumai, Belgium: Clinique des Deux Alices, Brussels, Belgium; A.Z. Middelheim. Anvers, Belgium: Hopital Civil de Jumet, Jumet, Belgium; Clinique Louis Caty, Baudour, Belgium: Hopital Methods d'Hayange, Hayange, Belgium; Hopital d'lxelies. Brussels, Belgium; Cenue Hospitalier Assays dcTivoli, Belgium: Centre Hospitaller Paul Brien, Brussels, Belgium: and Clinique de Braine-l'Alleud, Braine-l'Alleud, Belgium. The four evaluated markers were measured by commercially Address correspondence to Dr. Body, Institut Jules Bordet, Unit of Endocrinology, nie available radioimmunoassays; carcinoembryonic antigen Heger-Bordet I, 1000 Braxelles, Belgium. 190 Henry Ford Hosp Med J—Vol 37, Nos 3 & 4, 1989 CT and PDN-21 as Tumor Markers for Lung Cancer—Body et al Table 1 10000 Immunoreactive Calcitonin (iCT) and PDN-21 in Lung Cancer Percenlage of Percentiles (pg/raL) Highesi 'Values Elevated Values 50 95 99 (pg/raL) vs Nl vs BPD iCT All cases 65 948 7,800 9,998 18,9 13.7 SCLC 74 710 2,540 9,450 23.1 16.7 1000 NSCLC 58 1,048 7,800 9,998 15.6 11.3 PDN-21 All cases 14 630 4,410 14,500 44.2 26.1 SCLC 16 696 2,198 10,330 50.9 33.3 NSCLC 14 624 4,410 14,500 39.0 20.6 s I ..•t. to 84 years) and in 119 for PDN-2t (82 mates and 37 females; 100 median age 42 years, range 18 to 64 years). We defined the upper z^-- *••••• limits of normal values as the 95th percentiles determined in • - - I these groups, ie, 123 pglmL for iCT and 15.7 pglmL for PDN-2t. The 95th percenfiles for CEA and NSE were 7.5 ngl mL(n = 316) and ll.O ng/mL (n = 378), respectivety. Tumor marker specificity was determined in 88 patients with various benign pulmonary diseases (9) (54 males and 34 females; median age 63 years, range 19 to 87 years). Tumor markers were evaluated in 249 patients with advanced lung cancer (214 males and 35 females; median age 59 years, BPD SCLC NSCLC range 35 to 77 years). Of these patients, 210 had never been (n=142) treated before and 39 had recurrent disease after previous anti­ (n=108) neoplastic therapy (radiotherapy [n = 13], chemotherapy [n = 9], surgery [n = 4], or combined modalities [n = 13]), Tumor Fig 1—Serum concentrations of immunoreactive calcitonin types were as fotlows; 108 SCLC and 141 non-SCLC (NSCLC) (iCT) in patients with benign pulmonary diseases (BPD), smaU including 80 squamous cett lung cancers, 39 adenocarcinomata, cell lung cancer (SCLC), and non-small cell lung cancers 12 large cell lung cancers, and 10 other forms. (NSCLC). The upper Umd of normal (95 th percentile ofthe nor­ mal population) is represented by the dotted line. Results Seram CEA concentrations were elevated in 12% of the pa­ and PDN-21 did not conelate, the conetafion gradually im­ tients with benign pulmonary diseases, compared to 10% for proved as values increased (Fig 3; r^ = 0.60, P < O.OI). iCT and 9% for NSE or PDN-21, In this population, the 95th Not surprisingly, NSE was the most sensitive marker in pa­ tients with SCLC (83% had elevate•d values) wherea s* CEA was * • • percenfiles were 12.5 ng/mL for CEA, 183 pglmL for iCT, 11.6 ng/mL for NSE, and 24 pglmL for PDN-21. the most sensitive marker for •NSCL • * C« (50% had elevated val­ Individual values of iCT and PDN-21 measured in the three ues). However, PDN-21 provided some complementary infor­ groups of patients with benign pulmonary diseases, SCLC, or mation to that from the classical tumor markers. PDN-21 was NSCLC are depicted in Figs 1 and 2, respectivety.
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