Ampullary carcinoma: prognostic significance of ploidy, cell-cycle analysis and proliferating cell nuclear antigen (PCNA).
OBJECTIVE
The aim of the present study is to assess the nuclear DNA ploidy patterns, the fraction of cells in the various phases of the cell cycle as determined by flow cytometry and to evaluate Proliferative cell-nuclear antigen (PCNA) expression in order to examine the relationships between phase-two molecular factors, clinicopathological aspects and outcome of patients with cancers of the ampulla of Vater.


METHODS
Paraffin-embedded specimens from 18 cases of cancers of ampulla of Vater radically resected between 1985 and 1995 were analyzed by flow-cytometry and immunohistochemical staining with monoclonal antibody to the PCNA. The relationships between cell-proliferation kinetics, PCNA-positive cancer cells, clinicopathological findings and the clinical course were evaluated.


RESULTS
Pathologist reports documented 17 papillary adenocarcinomas and one case of mucinous carcinoma. According to the TNM classification, 4 patients were in stage I, 7 in stage II and 7 in stage III. Locally advanced ampullary tumors (T3-T4) had a significantly worse prognosis (p = 0.01); survival at 3 and 5 years for stage I-II patients (11 cases) was 90% and 79% as compared to 42% and 42% for patients with stage III (8 cases), respectively (p = n.s.). Thirteen cancers (72%) were diploid and 5 (28%) aneuploid. Patients with aneuploid tumors were younger (mean age: 59 years) than patients with diploid tumors (mean age: 66 years; p = 0.04). No significant correlation was found between size of the tumor (T), lymphnodal status (N), grading (G) or aneuploidy. Difference in terms of survival between aneuploid and diploid patients was relevant (16 vs. 121 months) but, due to the small number of cases, was not statistically significant (p = n.s). The mean value of S-phase fraction (SPF) was 14.8%. PCNA positive rate significantly correlates with size of the tumor (T1-T2 vs. T3-T4; p = 0.03). Actuarial overall survival resulted in 70%, 63% and 31% at 1, 5 and 10 years, respectively. The high rate of diploidy (72%) supports the relative benign behavior of ampullary cancers.


CONCLUSIONS
PCNA positive rate significantly correlates with size of the disease. Aneuploidy, although without significant prognostic value, correlates well with survival. Because of the wide range of all variables, more data are needed to establish the relationships between pathological factors, DNA ploidy and PCNA rate and their significance as molecular predictors of prognosis in ampulla of Vater cancers.
Crucitti
A
A
Department of General Surgery, Catholic University of the Sacred Heart, Rome, Italy. surgcic@mbox.vol.it
Masetti
R
R
Breccia
C
C
Coppola
R
R
Magistrelli
P
P
Nuzzo
G
G
Maggiano
N
N
Picciocchi
A
A
D000328:Adult; D000368:Aged; D014670:Ampulla of Vater / Q000473:pathology* / Q000601:surgery; D014408:Biomarkers, Tumor / Q000032:analysis*; D002453:Cell Cycle / Q000502:physiology*; D003138:Common Bile Duct Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011003:Ploidies; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D015996:Survival Rate; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D018809:Proliferating Cell Nuclear Antigen