Minichromosome Maintenance Protein (MCM6) in Low-Grade Chondrosarcoma: Distinction From Enchondroma and Identification of Progressive Tumors

Abstract

The distinction between chondrosarcoma and enchondroma is difficult, and no reliable immunohistochemical or molecular methods are available. Differentiation is important because the therapeutic consequences range from radiologic followup to radical operation. We studied 17 chondrosarcomas (12 grade 1) and compared them with 14 enchondromas immunohistochemically by using the monoclonal antibodies Ki-MCM6 (minichromosome maintenance protein 6), Ki-S5 (Ki-67), and Ki-S2 (repp86), in addition to the established clinical criteria. In comparison with the other markers, Ki-MCM6 proved more effective at identifying proliferative activity in grade 1 chondrosarcomas. The MCM6 labeling index correlated with tumor grade and was significantly increased in grade 1 chondrosarcomas compared with enchondromas. The 5 cases of progressive chondrosarcoma also had a significantly higher MCM6 labeling index than the nonprogressive cases. Furthermore, by means of the MCM6 labeling index, many cases of progressive disease were recognized among those of uncertain malignant potential, justifying their classification as low-grade chondrosarcomas.

Minichromosome maintenance protein 6, a proliferation marker superior to Ki-67 and independent predictor of survival in patients with mantle cell lymphoma

“…With the development of (Meng et al, 2001;Padmanabhan et al, 2004) and ovarian serous neoplasms (Scott et al, 2004) chondrosarcoma (Helfenstein et al, 2004), oligodendroglial tumours (Wharton et al, 2001(Wharton et al, , 2004, oesophageal neoplasm (Going et al, 2002), renal cell carcinoma (Dudderidge et al, 2005), breast cancer (Gonzalez et al, 2004), endometrial carcinoma (Li et al, 2005) and thyroid carcinoma (Guida et al, 2005).…”

“…Additional to the study by Ramnath, only few studies have investigated MCM proteins immunohistochemically. Brake et al (2003) focused on MCM7 in cervical cancer and Helfenstein et al (2004) on MCM6 in chondrosarcoma using the monoclonal antibody Ki-MCM6, also employed in our study.…”

“…Minichromosome maintenance protein 6 (MCM6) is one of six members (MCM2 -7) of the MCM family (Lindner et al, 2002) and consists of 821 amino acids with a molecular mass of 105 kDa (Heidebrecht et al, 2001). We have recently developed a specific monoclonal antibody against MCM6 (Ki-MCM6) (Heidebrecht et al, 2001) that enables the accurate detection of MCM6 in paraffin-embedded tissue (Heidebrecht et al, 2001;Helfenstein et al, 2004). Using Ki-MCM6, Heidebrecht et al (2001) showed that MCM6 is detectable in nucleosols or bound to nuclear chromatin during the entire cell cycle G1, S, G2 and M phases, but is absent in G0 phase (Labib et al, 2001).…”

“…The clinical relevance of MCM proteins as proliferation markers has been investigated immunohistochemically in several different malignant tumours (Freeman et al, 1999), for example, non-smallcell lung cancer (Ramnath et al, 2001), prostate cancer (Meng et al, 2001;Padmanabhan et al, 2004), oral squamous cell carcinoma (Kodani et al, 2003), chondrosarcoma (Helfenstein et al, 2004), oligodendroglial tumours (Wharton et al, 2001(Wharton et al, , 2004, oesophageal neoplasm (Going et al, 2002), renal cell carcinoma (Dudderidge et al, 2005), breast cancer (Gonzalez et al, 2004), endometrial carcinoma (Li et al, 2005) and thyroid carcinoma (Guida et al, 2005). Most of these studies focused on the detection of MCM2 (Freeman et al, 1999;Chatrath et al, 2003;Davidson et al, 2003;Kodani et al, 2003;Scott et al, 2004).…”

“…Most of these studies focused on the detection of MCM2 (Freeman et al, 1999;Chatrath et al, 2003;Davidson et al, 2003;Kodani et al, 2003;Scott et al, 2004). So far only few investigations studied MCM6 expression (Labib et al, 2001;Helfenstein et al, 2004).…”