Ovarian cancer is difficult to detect early, often called “the silent killer” because symptoms are vague and reliable screening tests are unavailable. For decades, the ovary was considered the primary source of this malignancy, leading to a focus on the ovarian surface. However, modern research now suggests that the most common and aggressive type of the disease actually begins in a different, adjacent structure. This shift in knowledge has profound implications for how the cancer is understood, prevented, and treated.
The Traditional View Versus Modern Understanding
The historical model assumed ovarian cancer originated in the surface epithelial cells covering the ovary. This theory was based on the fact that most tumors are found growing on and within the ovary at diagnosis. Observations, such as the link between frequent ovulation and increased risk, supported the idea that repeated injury to the ovarian surface led to cancerous changes.
This traditional view has been challenged by pathological and molecular analysis. It is now widely accepted that High-Grade Serous Carcinoma (HGSC), which accounts for 70 to 80% of all epithelial ovarian cancers and is the most lethal form, does not typically start in the ovary. The consensus points to the distal end of the fallopian tubes, specifically the fimbriae, as the site of origin for most HGSC cases.
The tissue lining the fallopian tubes, the fallopian tube epithelium, shares a similar embryologic origin with the cells that line the ovary. This similarity allows malignant transformation to begin in the tube before the disease spreads.
Identifying the Precursor Lesion
The specific microscopic lesion preceding most HGSC development has been identified within the fallopian tube. This pre-invasive change is called Serous Tubal Intraepithelial Carcinoma (STIC), and it is considered the true starting point for the majority of these aggressive cancers. STIC is a cluster of highly abnormal cells confined to the lining of the fallopian tube, usually located at the fimbriated end, the projections closest to the ovary.
STIC identification relies on specific molecular markers, notably the presence of an aberrant p53 protein expression, often called a “p53 signature.” This indicates a mutation in the TP53 tumor-suppressor gene, an early step in the carcinogenic process. Once these abnormal cells form, they can detach from the fimbriae and spread.
The fimbriae are open-ended structures, allowing cells to shed easily into the pelvic cavity. These abnormal cells can then implant onto the adjacent ovary or the peritoneum, the lining of the abdominal cavity. Once implanted, the cells grow into what is clinically diagnosed as advanced “ovarian” or “peritoneal” cancer.
Impact on Prevention and Risk Reduction
The discovery that the fallopian tube is the source of HGSC has fundamentally changed strategies for cancer prevention. For women with a high genetic risk, such as those with BRCA1 or BRCA2 gene mutations, the standard prevention remains a Risk-Reducing Salpingo-Oophorectomy (RRSO). This procedure involves the removal of both the ovaries and the fallopian tubes, offering the highest level of protection against both ovarian and breast cancers.
RRSO induces immediate surgical menopause when performed before natural menopause. This can lead to complications like bone loss and cardiovascular risks.
For average-risk women who wish to reduce their cancer risk without the side effects of immediate menopause, a procedure called Opportunistic Salpingectomy (OS) is gaining widespread acceptance. OS involves the surgical removal of only the fallopian tubes while intentionally leaving the ovaries intact.
Opportunistic salpingectomy is performed when a woman is already undergoing another pelvic or abdominal surgery, such as a hysterectomy for benign disease or a tubal ligation for sterilization. By removing the fallopian tubes, surgeons eliminate the primary tissue where HGSC is thought to originate, potentially reducing the risk of this specific cancer by up to 80%. This strategy is attractive because it avoids the hormonal consequences of removing the ovaries.
Other Origins of Ovarian Cancer
While HGSC is the most common form of the disease, it is important to recognize that not all ovarian cancers originate in the fallopian tubes. Ovarian cancer is a heterogeneous group of diseases, and other subtypes have distinct origins and different biological behaviors. These non-serous cancers are often grouped as Type I ovarian tumors, in contrast to the Type II HGSC.
Endometrioid and clear cell carcinomas are two such subtypes, and they are frequently associated with a prior history of endometriosis. These tumors are thought to develop from precursor lesions within endometriotic cysts on the ovary. Mucinous carcinomas, another less common subtype, often arise from different processes.
The fallopian tube origin applies predominantly to the high-grade serous type, which accounts for the majority of mortality. The discovery of the fallopian tube’s role has clarified the biology of the most aggressive form of “ovarian” cancer.