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

Results

Data was collected from 32 cases, including 19 malignant and 13 benign cases. P53 immunostain was positive in 5 cases, while 27 cases were negative (Table 2). Eight mutation patterns (different from normal control) were detected by SSCP. Five of these were confirmed by sequencing (Figure 1).

Figure 1.

Example data from single-strand conformation polymorphism with sequence confirmation. The band alterations compared to normal patterns (WT) are indicated by arrows. The SSCP mutation detected in specimen 5 was also detected as a leu to phe mutation at amino acid position 206 (left). The SSCP mutation detected in specimen 7 was also detected as an arg to ser mutation at amino acid position 202 (right).

Two of three high grade invasive tumors with positive p53 immunostain had a mutation band pattern by SSCP, 2 of which were in exon 6. TP53exon 6 sequencing confirmed the presence of these mutations (Table 3).

Only one malignant case with p53 positive immunostain had a negative SSCP. This case was of a patient with a history of an ovarian mass, with extensive peritoneal involvement and a positive peritoneal fluid cytology for high grade serous carcinoma. However, the patient underwent chemotherapy, and radiation therapy before surgery (total hysterectomy and bilateral salpingo-oophorectomy, omentectomy and lymphadenectomy). Histologically, the only evidence of tumor was few foci of high-grade serous carcinoma present within the lymphatic channels in the peritoneum.

There were 2 histologically benign cases in which p53 immunostain was positive in the fallopian tubes (Figure 2). These lesions represent what is described in the literature as serous tubal intraepithelial lesions (STILs) or p53 signature, as in the areas were p53 immunostain was positive, the epithelium was not stratified and was histologically normal. These 2 cases showed mutation band patterns in exon 6 by SSCP (Table 3) that were not detected by sequencing.

Figure 2.

p53 immunostain labeling of serous tubal intraepithelial lesions and small endometrial serous adenocarcinoma. (a) First case of serous tubal intraepithelial lesion (p53 immunostain, 200X). (b) Second case of serous tubal intraepithelial lesion (p53 immunostain, 100X). (c) Small endometrial serous adenocarcinoma (H&E, 200X). (d) Strong positivity for p53 immunostain in the small endometrial serous adenocarcinoma (p53 immunostain, 200X).

From the 15 malignant tumors with negative p53 immunostaining, only 3 cases had a mutation band pattern by SSCP. These cases were FIGO stage I and grade 1–2 endometroid endometrial adenocarcinomas. The patients were 72, 53, and 49 years old.

Among the 11 cases with benign histology and negative p53 immunostain, 1 case had a mutation band pattern in exon 6 by SSCP (Table 3). This case was a 50 year-old patient who underwent total hysterectomy and bilateral salpingo-oophorectomy for a benign condition and had an absolutely benign histology. P53 immunostain was negative in the sections from the fallopian tubes.

Based on this data, the sensitivity, and specificity of SSCP in detecting TP53 mutations in the mucus in high grade malignancies are 80 and 85% respectively. The sensitivity of SSCP increases to 100% if we exclude the case of high grade tumor that was confined to the peritoneum, while the specificity remains 85%. However, the sensitivity and specificity of SSCP in detecting only invasive high grade carcinomas are 66 and 79% respectively.

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