Page 111 - Read Online

Page 4 of 20 Vidoni et al. J Cancer Metastasis Treat 2021;7:4 I http://dx.doi.org/10.20517/2394-4722.2020.95

Figure 2. Ovarian cancer. Schematic representation of ovarian cancer histological types and associated gene alterations. HER2: human
epidermal growth factor receptor 2; PTEN: phosphatase and tensin homolog

the genetic lesion pattern and, consequently, on the clinical features, ovarian cancers are categorized as
type I or type II, the former arising from the ovary and the latter arising from the Fallopian tube or the
[26]
ovarian surface epithelium . Type I tumors, which include LGS, mucinous, endometrioid, clear cell,
and transitional cell carcinomas, carry few mutations, are TP53 wild-type and show an indolent clinical
behavior. In contrast, type II tumors, which include HGS ovarian cancer, undifferentiated carcinomas and
carcinosarcomas, are genetically highly unstable with mutated TP53 and dysfunctional BRCA1/2, in the
majority of cases, and show a very aggressive and metastatic behavior. Standard management of ovarian
cancer comprises of a maximal cytoreductive surgery as a first line of intervention; the second therapeutic
approach involves treatments with a combination of chemotherapeutic agents, such as platinum-containing
drugs (cisplatin and carboplatin) and taxane drugs family (paclitaxel and docetaxel) and, as a second line,
[27]
with gemcitabine, doxorubicin, and bevacizumab .

Endometrial cancer
Endometrial cancer is the third malignancy, in terms of incidence among female cancers , and the most
[16]
[28]
prevalent female cancer among the American women .

Endometrial cancers are associated with sporadic mutations of several oncogenes and tumor suppressor
[29]
genes, among which PTEN, PI3KCA, KRAS, TP53, and CTNNB1 are the most frequent . Women affected
by the Lynch syndrome with MLH1 and MSH2 gene mutations are more susceptible to developing
endometrial cancer . Endometrial cancers are classified into seven different histological subtypes: (1)
[30]
endometrioid carcinoma, accounting for 80% of total endometrial cancer; (2) mucinous adenocarcinoma
(1%-9%); (3) serous carcinoma (less than 10%); (4) clear cell carcinoma (less than 5%); (5) neuroendocrine
[31]
carcinoma; (6) mixed carcinoma; and (7) undifferentiated and dedifferentiated carcinoma [Figure 3].
PTEN, PIK3CA, and ER/PR are the most frequently mutated in endometrioid adenocarcinoma, while TP53
[32]
and E-cadherin are the more common mutated genes in serous carcinoma . As for the management and
prognosis, the majority of endometrial cancers (particularly, grades I and II endometrioid carcinomas)
usually remain confined into the uterine corpus and can be removed surgically, thus having overall a good
prognosis. On the contrary, serous, clear cells, grade III endometrioid, and undifferentiated carcinomas are
more aggressive, often diagnosed at advanced stages with metastasis, require a more complex treatment
[33]
combining surgery, radiotherapy and hormone/chemo/molecular therapies [Figure 3].
Cervical cancer
[16]
Cervical cancer is the second classified tumor for incidence and mortality among female malignancies .

Cervical intraepithelial cells determine three grades of dysplasia, defined as cervical intraepithelial
[34]
neoplasia 1 (low-grade), 2 (moderate grade), and 3 (high-grade), before becoming invasive cancer . The