Detection Frequency of p53 Signatures in Fallopian Tubes from Women with BRCA 1 or 2 Mutations (BRCA+) and Controls: The Role of Serial Sections
KK Mehra, M Chang, AK Folkins, C Raho, L Yuan, M Mehrad, SS Tworoger, CP Crum, A Saleemuddin. Brigham and Women's Hospital, Boston, MA; University of Toronto, Toronto, ON, Canada; Stanford, Palo Alto, CA
Background: The p53 signature in the distal fallopian tube has been proposed as an early precursor to pelvic serous carcinoma, but its absolute and relative frequency in BRCA positive or negative women has been controversial. Precise ascertainment of the frequency is critical to determining the risk factors for this entity in either population.
Design: 24 BRCA+ and 40 controls (women with non-malignant disorders) were studied. In each case, three serial sections from every tissue block from each fallopian tube were removed from the block. Following sectioning through 100-200 microns, an additional three serial sections were placed on slides followed by an additional three serial sections following another 100-200 microns. One slide from each round was stained for p53. The number of cases, total blocks, proportion of blocks with signatures seen in each of the three rounds, and proportion of blocks with more than one signature detected following staining of the three sections were recorded. Comparisons were analyzed by chi-square.
Results: 17 (71%) and 20 (50%) of BRCA+ and control tubes harbored p53 signatures following the sectioning protocol outlined above (p = .12); 21 and 33% of all tissue blocks sectioned harbored signatures from the two groups (p = .07) respectively. In 49 and 32 per cent of p53 signature positive cases in the two groups, the p53 signatures were not discovered until the second or third round of sectioning. Thirty eight and 40% of BRCA+ and control subjects harbored p53 signatures in more than one focus in a single block.
Conclusions: p53 signatures are more common than previously reported and the frequency of detection increases as a function of sectioning through the tissue block, both in absolute frequency and in numbers of p53 signatures detected in a given block. There is a trend for a higher absolute frequency of p53 signatures (71 vs 50%; p = .12) in BRCA+ subjects, but this is not reflected in a greater number of p53 signatures or positive blocks per case. This study underscores the importance of systematic immunohistochemical examination of fallopian tubes when comparing the frequency of p53 signatures in different populations. Attention to this detail is critical when exploring risk factors germane to early serous carcinogenesis.
Category: Gynecologic & Obstetrics
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 146, Tuesday Afternoon