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Research Article

Microscopic and Early-Stage Ovarian Cancers in BRCA1/2 Mutation Carriers: Building a Model for Early BRCA-Associated Tumorigenesis

Melinda S. Yates, Larissa A. Meyer, Michael T. Deavers, Molly S. Daniels, Elizabeth R. Keeler, Samuel C. Mok, David M. Gershenson and Karen H. Lu
Melinda S. Yates
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Larissa A. Meyer
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Michael T. Deavers
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Molly S. Daniels
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Elizabeth R. Keeler
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Samuel C. Mok
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David M. Gershenson
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Karen H. Lu
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DOI: 10.1158/1940-6207.CAPR-10-0266 Published March 2011
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    Figure 1.

    A, microscopic high-grade serous carcinoma near the surface of the ovary (case 2); boxes indicate area shown at higher magnification in B and C.

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    Figure 2.

    Possible pathways of BRCA-associated ovarian/fallopian tube cancer initiation and progression. A, some tumors begin in the fallopian tube and continue to grow larger, while remaining confined to the tube, creating a primary tubal cancer. However, because of the close association between the fimbria and ovarian surface, fallopian tube tumor cells could also spread to the ovary (B and C). B, cancer initiation occurs in the fallopian tube fimbria and a small number of cancer cells are deposited on to the ovarian surface, which provides a supportive environment for tumor growth. C, because of the cyclic rupture, repair, and invaginations that occurs with ovulation, cancer cells from the fimbria can be transferred into the ovarian stroma where it grows and expands. D, alternatively, early carcinogenic changes may occur within ovarian cysts where the tumor grows, again producing a dominant ovarian mass. As the tumor grows larger, involving both the fallopian tube and the ovaries, it becomes difficult to identify whether the site of origin was ovary or fallopian tube. OSE, ovarian surface epithelium.

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  • Table 1.

    Microscopic cancers identified at the time of RRSO for BRCA mutation carriers

    Case no.Age at RRSO, yBRCA1/2 mutationPrimary siteHistologyWashings
    151BRCA1Primary peritoneal (washings only)Washings–HGSCa. No carcinoma identified in ovaries or fallopian tubesHGSCa
    253BRCA1OvaryHGSCa near the surface of the ovary (1 mm)NE
    360BRCA1Fallopian tube2 foci of HGSCa involving the fimbria of RFT, confined to mucosa (1.7 and 0.4 mm)Negative
    452BRCA1Fallopian tube2 foci of HGSCa confined to mucosa in RFT, first focus is in tube proper (1 mm), second focus in fimbria (0.4 mm)Negative
    570BRCA1Fallopian tubeHGSCa involving the fimbria, confined to mucosa (2 × 3 mm)Negative
    655BRCA1Fallopian tubeHGSCa involving fimbria comprising mucosa and submucosa (2 mm)Negative

    Abbreviations: NE, not evaluated; RFT, right fallopian tube.

    • Table 2.

      Literature review of microscopic ovarian, fallopian tube, and peritoneal tumors in BRCA1/2 mutation carriers

      IDBRCA1/2 mutationPrimary siteWashingsReference
      L1BRCA1Fallopian tubePositive18
      L2BRCA1Fallopian tubeNegative19
      L3BRCA1Fallopian tubeNegative19
      L4BRCA1Fallopian tubeNegative19
      L5BRCA1Fallopian tubeNegative9
      L6BRCA1Fallopian tubeNegative9
      L7BRCA1Fallopian tubeNegative9
      L8BRCA1Fallopian tubeNegative9
      L9BRCA1Fallopian tubeNegative10, 20
      L10BRCA1Fallopian tubeNegative11
      L11BRCA1Fallopian tubeNegative11
      L12BRCA1Fallopian tubeNegative21
      L13BRCA1Fallopian tubeNegative21
      L14BRCA1Fallopian tubePositive12, 21
      L15BRCA1Fallopian tubePositive12, 21
      L16BRCA1Fallopian tubeNR14
      L17BRCA1Fallopian tubeNR14
      L18BRCA1Fallopian tubePositive15
      L19BRCA2Fallopian tubePositive19
      L20BRCA2Fallopian tubeNegative19
      L21BRCA2Fallopian tubeNegative12, 21
      L22BRCA2Fallopian tubeNegative15
      L23BRCA2Fallopian tubeNegative15
      L24BRCA1OvaryPositive10, 20
      L25BRCA1OvaryNR13
      L26BRCA1OvaryNR14
      L27BRCA1OvaryNR14
      L28BRCA1OvaryNegative15
      L29BRCA2OvaryNR13
      L30BRCA1Both ovariesNegative9
      L31BRCA1Both ovariesNegative11
      L32BRCA1Both ovaries, 1 fallopian tubeNegative10
      L33BRCA1Both ovaries, 1 fallopian tubePositive10, 20
      L34BRCA1Both ovaries, 1 fallopian tubeNR13
      L35BRCA1Ovary and fallopian tubeNegative19
      L36BRCA1Ovary and both fallopian tubesNR14
      L37BRCA2Both ovaries and 1 fallopian tubeNegative11
      L38BRCA2Primary peritonealNegative10

      Abbreviation: NR, not reported.

      • Table 3.

        Early-stage ovarian or fallopian tube cancers identified in BRCA mutation carriers

        Case no.Age at diagnosis, yBRCA1/2 mutationGradeDominant massHistologyBilateral or unilateral?Primary sizeStage
        732BRCA1HighOvarySerous carcinomaBilateral12 × 6 × 6 cmIB
        843BRCA1HighOvarySerous carcinomaUnknownUnknownIIA
        956BRCA1HighOvarySerous carcinomaBilateral11 cmIC
        1055BRCA1HighOvarySerous carcinomaUnilateral8 cmIIC
        1154BRCA1HighOvaryUndifferentiated carcinomaUnilateralUnknownIA
        1250BRCA1HighFallopian tubePoorly differentiated carcinomaUnilateral2 cmIA
        1340BRCA1HighFallopian tubeSerous carcinomaUnilateral8 × 5 × 3 cmII
        1450BRCA1HighFallopian tubeSerous carcinomaUnilateral2 × 1 × 1 cmIA
        1554BRCA2HighOvaryPoorly differentiated carcinomaUnilateral7 × 7 × 5 cmIIB
        1659BRCA2HighOvarySerous carcinomaBilateral7 cmIIC
        1755BRCA2HighOvarySerous carcinomaBilateral14 × 7 × 6 cmIB
        1850BRCA2HighOvarySerous carcinomaBilateral7 × 5 × 3 cmIIA
        1961BRCA2HighOvarySerous carcinomaUnilateral15 cmIIA
        2041BRCA1 and BRCA2HighOvarySerous carcinoma involving left ovary and detached fragments in RFT lumenUnilateral6 cmIIB

        Abbreviation: RFT, right fallopian tube.

        Additional Files

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        Cancer Prevention Research: 4 (3)
        March 2011
        Volume 4, Issue 3
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        Microscopic and Early-Stage Ovarian Cancers in BRCA1/2 Mutation Carriers: Building a Model for Early BRCA-Associated Tumorigenesis
        Melinda S. Yates, Larissa A. Meyer, Michael T. Deavers, Molly S. Daniels, Elizabeth R. Keeler, Samuel C. Mok, David M. Gershenson and Karen H. Lu
        Cancer Prev Res March 1 2011 (4) (3) 463-470; DOI: 10.1158/1940-6207.CAPR-10-0266

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        Microscopic and Early-Stage Ovarian Cancers in BRCA1/2 Mutation Carriers: Building a Model for Early BRCA-Associated Tumorigenesis
        Melinda S. Yates, Larissa A. Meyer, Michael T. Deavers, Molly S. Daniels, Elizabeth R. Keeler, Samuel C. Mok, David M. Gershenson and Karen H. Lu
        Cancer Prev Res March 1 2011 (4) (3) 463-470; DOI: 10.1158/1940-6207.CAPR-10-0266
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