Abstract
BackgroundSerous tubal intraepithelial carcinoma (STIC) and the p53 signature in tubal mucosa have been supported to be precursor lesions in high-grade serous carcinoma (HGSC) of the fallopian tube, ovary, and peritoneum. It remains critical to find biomarkers for precursor lesions in order to detect HGSCs efficiently. IMP3 is an oncoprotein that has been explored in human malignancies. No studies have specifically addressed the expression of IMP3 in precursor or early lesions of HGSC. The main purposes of this study are to evaluate if IMP3 plays any role in the process of pelvic serous carcinogenesis by examining its expression in HGSC precursor lesions, to examine the relationship between IMP3 and p53 in those precursor lesions, and to check if IMP3 can be used as a biomarker for early diagnosis.MethodsImmunohistochemistry for IMP3 and p53 was performed and evaluated in 48 HGSCs with STIC, 62 HGSCs without STIC, and 60 benign cases as negative controls. Sections of fallopian tubes with or without STIC , as well as cancers within the ovaries, were studied. IMP3 signature was defined as strong IMP3 cytoplasmic staining in 10 or more consecutive benign-looking tubal epithelial cells. The relationship between IMP3 and p53 overexpression was examined.ResultsIn the 48 HGSC patients with STIC, IMP3 was positive in 46% of STIC lesions and had a similar positive rate in the invasive components of HGSC. IMP3 was also expressed in normal appearing tubal epithelia (IMP3 signature) in 15 (31%) of 48 HGSC cases with STIC and 10 (16%) of 62 cases without STIC. In contrast, no single IMP3 signature was found in the benign control group. Concordant expression of IMP3 and p53 signatures in the STIC group was found in up to one-third of the cases. There were also five (10%) STIC cases with positive IMP3 and negative p53.ConclusionsWe conclude that IMP3 may be involved in the process and progression of pelvic HGSC and may serve as a complimentary biomarker in diagnosing STIC.
Highlights
Pelvic serous cancer (PSC), including mainly high-grade serous carcinoma (HGSC) that involves the primary sites of the ovary, the fallopian tube, and the peritoneum, is the most common and lethal type of müllerian malignancy, comprising more than 70% of all malignancies from these organs [1,2,3]
Patient characterization This study examined IMP3 expression in the fallopian tubes of patients from the following three groups: HGSC with Serous tubal intraepithelial carcinoma (STIC), HGSC without STIC, and benign controls
The HGSC with STIC group included 48 patients who were identified by STIC in the fallopian tubes
Summary
Pelvic serous cancer (PSC), including mainly high-grade serous carcinoma (HGSC) that involves the primary sites of the ovary, the fallopian tube, and the peritoneum, is the most common and lethal type of müllerian malignancy, comprising more than 70% of all malignancies from these organs [1,2,3] Effective management of this disease has been hampered because up to 90% of HGSC in patients are remain in the tubal epithelial layer. Tubal high-grade serous carcinogenesis remains elucidated, alteration of TP53 is a well-known gene that plays a key role for cancer initiation and development [13] This was supported by the finding of p53 signatures, defined as intense p53 protein overexpression in the normal looking tubal epithelia [9]. The main purposes of this study are to evaluate if IMP3 plays any role in the process of pelvic serous carcinogenesis by examining its expression in HGSC precursor lesions, to examine the relationship between IMP3 and p53 in those precursor lesions, and to check if IMP3 can be used as a biomarker for early diagnosis
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