DCC expression is related to mucinous differentiation but not changes in expression of p21WAF1/Cip1 and p27Kip1, apoptosis, cell proliferation and human papillomavirus infection in uterine cervical adenocarcinomas

Abstract

To clarify possible roles of DCC expression in tumour differentiation and cell kinetics, we immunohistochemically investigated 80 uterine cervical adenocarcinomas (C-ACs), including 31 mucinous (M) and 31 endometrioid (E) lesions, and 18 adenocarcinomas in situ (AIS), along with 39 normal cervical samples. The results were compared with findings for p21 WAF1/Cip1 and p27 Kip1 expression, apoptosis, cell proliferation and human papillomavirus (HPV) infection. Nine C-AC cases were also examined using a combination of the reverse transcription-polymerase chain reaction and Southern blot hybridization, as well as Western blot assays. Significantly decreased DCC scores were observed in E-ACs but not M-ACs, as compared to normal cervical glandular epithelia and AIS. Average p21 WAF1/Cip1 and p27 Kip1 scores were significantly higher in E-ACs than M-ACs, in line with high apoptotic, mitotic and Ki-67 labelling indices. A concordance of the results for DCC and p21 WAF1/Cip1 expression between mRNA- and protein-based assays was also noted. Change of DCC expression, however, was not related to any of the cell kinetic markers or clinicopathological features in ACs of either type. There was also no association with the HPV status, although infection was significantly linked with high values for cell kinetics. These results suggest that DCC expression in C-ACs is closely associated with mucinous differentiation. © 1999 Cancer Research Campaign

Role of cell‐cycle regulatory proteins in gynecological cancer

“…Weak immunostaining was mainly detected in mucinous and adenosquamous carcinomas (Milde‐Langosch et al, 2001d). This is in accordance with Saegusa et al who found higher p27 scores in endometrioid than in mucinous AC (Saegusa and Okayasu, 1999). While we and others did not observe an association of p27 expression with HPV infection rate, we found a significant correlation of p27 levels with HPV 16/18 E6/E7 oncogene expression (Milde‐Langosch et al, 2001d).…”

“…Most studies described above dealed with squamous cervical lesions and only a minority of AC were examined. The few reports on AC agree in that they describe nuclear p27KIP1 immunoreactivity in a high percentage of invasive AC as well as ACIS (Lu et al, 1998,1999; Saegusa and Okayasu, 1999; Milde‐Langosch et al, 2001d). In our own study, p27 staining was observed in all analyzed AC with varying staining intensities and different proportions of positive tumor cells.…”

“…In contrast to Lu et al (1998), who found a better overall survival rate in patients with p21‐positive AC than in p21‐negative cases, Cheung et al (2001a) demonstrated that p21 expression significantly correlated with advanced disease stage and negative HPV results. In most studies, however, there was no significant association of p21 expression and clinico‐pathological factors or prognosis (Kim et al, 1998c; Saegusa and Okayasu, 1999; Skomedal et al, 1999; Bae et al, 2001; Graflund et al, 2002a,b).…”

Absence of Human Papillomavirus Infection in Minimal Deviation Adenocarcinoma and Lobular Endocervical Glandular Hyperplasia

“…Although the incidence of SCC has declined, adenocarcinoma (AC), which accounts for approximately 10 to 30% of cervical carcinomas, has remained the same or increased in some countries (6)(7)(8)(9)(10). Some studies have also shown a high incidence of HPV in AC (43.8-94%) and adenocarcinoma in situ (56.3-100%) (11)(12)(13)(14)(15).…”

Age-dependent differences in tumor cell polarity in endometrial carcinomas

“…Positive control sections known to contain p21 or p53, respectively, were used (Saegusa and Okayasu 1999;Saegusa et al 2000). For p27 and two hormone receptors, stromal components or infiltrating lymphocytes were applied as internal controls.…”