Adenocarcinoma arising from the cervix and the endometrium in our series shows overlapping clinicopathological presentations. The youngest patients for both cancers were 30 years of age though the mean age of endocervical adenocarcinoma is about five years younger. There was a number of adenocarcinomas of the cervix which was in the mean age of adenocarcinoma of endometrium. These two cancers also have similar ethnic distribution. The ethnic distribution of our cases is comparable with the background population implying fair representation of the sampling population. They are more seen among the ethnic Malay than other ethnic groups in this series depicting the ethnic distributions of the community served by the two hospitals.
We noted that certain clinicopathological parameters were significantly associated with other parameters within the same cancer. For adenocarcinoma of the cervix, the age of the patients was significantly associated with tumor size and with depth of infiltration. The histologic grade was strongly associated with presence of lymph node metastasis. FIGO staging was strongly associated with presence of corpus infiltration, vascular invasion, and lymph node metastasis. For adenocarcinoma of endometrium, the age of the patients was associated with menopausal status, FIGO staging with histological grading of the cancer, and presence/absence of myometrial invasion.
When these clinicopathological parameters were tested against the expression of the three cell cycle markers, none of the clinicopathological parameters of adenocarcinoma of the cervix including the histologic subtypes had significant association with p16INK4a expression alone. However, when p16INK4a expression and p27Kip1 expressions were analyzed in combination, there were strong associations with presence/absence of lymph node metastasis. p21WAF1 expression alone is significantly associated with infiltration of the corpus and lymph node metastasis. Lymph node involvement was also significantly associated with p27Kip1 expression. For adenocarcinoma of endometrium, only P16INK4a expression had strong association with the histologic grade. p21WAF1 and p27Kip1 expressions were not significantly associated with any clinicopathological parameters. Our study shows that we could use these cell cycle markers as predictors for more aggressive subsets of adenocarcinomas of the cervix and endometrium.
There are a number of studies which have utilized the use of cell cycle regulatory genes such as P16INK4a, p21WAF1, and p27Kip1 in predicting the behavior of certain cancers such as malignant astrocytomas [23
], oral squamous cell carcinomas [24
], vulval carcinomas [25
], and primary large-cell neuroendocrine carcinoma of the parotid gland [26
]. In the latter, markedly reduced expressions of p21Waf1 and p27Kip1 were noted in the salivary gland cancer cells indicating highly aggressive biologic behavior [26
]. Methylation of p16INK4a was seen to be correlated with gender and tumor size (P
= 0.005 and P
= 0.035, resp.) in colorectal carcinoma (CRC) and could be used as a marker of poor prognosis in CRC [27
]. In 224 vulvar squamous cell carcinomas stained with p16, p21, and p27, Knopp et al., noted a high expression of p16 as indicator of a better prognosis in the multivariate analysis (RR = 0.5, 95% CI = 0.2–1.0) and less risk of developing lymph node metastasis (OR = 0.3, 95% CI = 0.2–0.7) [25
]. They also noted that a high level of p21 was significantly associated with shorter survival in patients staged FIGO I and II (RR = 3.4, 95% CI = 1.3–9.3). We could not find any published literature on utilizing the use of these markers on adenocarcinoma of the cervix and endometrium
In conclusion, for adenocarcinoma of the cervix, p21WAF1 expression is significantly associated with infiltration of the corpus and lymph node metastasis. p27Kip1 expression is significantly associated with lymph node invasion. The presence of lymph node metastasis is strongly associated when p16INK4a and p27Kip1 expressions are analyzed in combination. For adenocarcinoma of the endometrium, p16INK4a expression is associated with histologic grade but not histologic type. Our study shows that we could use these cell cycle markers as predictors for more aggressive subsets of adenocarcinoma of the cervix and endometrium.