Use of Cervical Mucus to Screen for Gynecological Malignancies

A Pilot Study

Ihab Lamzabi; Lela Buckingham; Mezgebe Gebrekiristos; Richa Jain; Paolo Gattuso; Vijaya Reddy; Alfred Guirguis; Summer Dewdney; Jacob Rotmensch; Pincas Bitterman

Disclosures

Mod Pathol. 2013;26(11):1508-1513. 

In This Article

Discussion

The results of this study provide sufficient evidence that DNA from high-grade precancerous and cancerous lesions can be detected in the cervical mucus. In addition, SSCP detected potential precancerous lesions in the fallopian tube which suggests that it might detect very early events in fallopian tube and ovarian cancer development.[8–10] We could not include cases of high-grade carcinomas of the ovary as the cases we received within our inclusion period had involvement of the serosal surface. The only ovarian cancer we could include was a stage 1 clear cell carcinoma that was negative for p53 immunostain, and had no identifiable TP53 mutation pattern by SSCP.

Our main limitation with the results of this study is that it was done in a post operative setting, which could have caused contamination of the cervical mucus despite our cautious handling of the material. However, such contamination is less likely to explain the positive SSCP in patients with precancerous lesions (STIL) in the fallopian tubes or very small malignancies confined to the uterine cavity.

The study included cases of low-grade endometrial endometrioid adenocarcinomas that were p53 negative by immunohistochemistry but showed TP53 mutation in the mucus. This could be explained by the sporadic mutations that occur in cancer cells that might have been detected in the mucus.

One case of a benign uterus showed TP53 mutation by SSCP and DNA sequencing. We think that this patient might have a precancerous lesion that was not detected by routine histology and was not present in the sections stained with p53 antibody.

The second step of this project will be a prospective study. We plan to collect cervical mucus from patients with suspected malignancies and suspected benign diseases in preoperative consultations. We will seek to detect different genetic and environmental markers using molecular genetics methods in conjunction with mass spectrometry. This will help us extend our research to other proteins, and molecules. The theory behind the use of mass spectrometry in analyzing the mucus of cancerous lesion lies in the tumor invasion of the basement membrane into the stroma, which will cause destruction and leakage of connective tissue molecules. In addition, neoplastic epithelium is more friable and apoptotic than the atrophic epithelium of postmenopausal women. The study and analysis of different molecules from epithelium, and stroma in both malignant and benign tumors might allow us to identify profiles that help distinguish normal mucus and mucus contaminated with malignant tumor and its environment. When an adequate database is established, we can initiate the third step of the project which will consist of a large-scale prospective study that will include women over the age of 50. The mucus sample can be taken in conjuction with routine Pap smears or routine medical checkups. The cases will then be screened using the biomarker(s) and method(s) studied in step 2 that showed the highest sensitivity, and efficiency. The positive cases will be subject to a profiling that will determine the risk of the patient of having a malignancy versus precancerous lesion, its type, and possibly its location.

Although we started our study with minimal resources to explore the possibility to screen for high grade gynecological malignancies using cervical mucus, the recent publication by Kindle I et al[14] supports our theory and the findings of our study. Moreover, our results bring additional findings. We demonstrated that precancerous gene mutations could also be detected. The impact of mutational analysis on an eventual screening test using DNA content of cervical mucus still needs to be investigated. Finally, combined efforts of the medical and scientific community could confirm these results and improve the sensitivity of using cervical mucus as a screening test.

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