The Rise and Fall of STIC

Chris Crum data:

2007: STIC is found in most cases of high-grade serous carcinomas. (AJSP).

2015: STIC is found in only 40% of high-grade serous carcinomas. (AJSP)

2022: STIC is found in 17.5% of high-grade serous carcinomas. (J of Path)

What happened? The proposed theory that high-grade serous carcinomas arise in the fallopian tube epithelium was not based on solid grounds.

Carcinomas are epithelial tumors, and the only part of the gynecologic tract with serous epithelium is the fallopian tube. Therefore, it seems reasonable to think that extrauterine serous carcinomas must be from the fallopian tube epithelium. However, if we do not accept the mesenchymal-epithelial transition as another possibility for serous epithelia, we will not understand how the epithelial areas of the Mullerian tract develop. The endometrium, the fallopian tube, and the mesothelial surface, have epithelial cells but, they originated in the mesenchyma. This transition can be repeated in neoplasms.

Comparing the origin of extra uterine serous tumors in the fallopian tube vs in the ovary, the following facts argue against an origin in the fallopian tube.

1- This theory has been based on diagrams, there is no one photo documenting this. Diagrams leave a lot of room for imagination and virtual theories can be created.

2- There is no explanation about how the cells from the fallopian tube get in the stroma of the ovary. The diagram proposing that the cells from the FT get inside the ovary after ovulation is ridiculous bc we never see endosalpingiosis in the copus luteum or in the corpora albicans. Foci of endosalpingiosis are always in the stroma, unrelated to other component of the ovarian parenchyma. In addition, there are cases of a STIC in one side and the ovary with tumor is the opposite side.

3- There are two excellent animal models of ovarian cancer, one natural, the chicken, and one induced with hormones, the guinea pig. There are no animal models supporting the origin from the fallopian tube.

4- Extra uterine serous neoplasms are all related, independently of their grade. It is not unusual to find a serous high-grade carcinoma associated with a serous adenofibroma. There are reports of high-grade serous carcinoma associated with serous borderline tumors, or with a low-grade serous carcinoma. It is difficult to accept that the fallopian tube is the origin of high-grade serous carcinoma, but not the origin of the other types of serous tumors.

5- It is very easy to explain the known facts associate with extrauterine serous carcinomas, like the protection of contraceptives or breast feeding, accepting the origin in the ovary.

It is difficult to explain this with the fallopian tube theory.

6- One of the pillars supporting the origin of serous carcinoma from the fallopian tube is clonality. However, clonality is a circus, it should be called “clownality”. Different authors have unusual interpretations of clonality, for example: in the bladder clonality means multicentricity, but in the endometrium and ovary is an indication of “good metastases”, and in the ovary and peritoneum is a “bad metastasis”. You can read more about “clownality” in another blog in my site.

7- Based on the theory that the origin of ovarian cancer is in the fallopian tube a risk-reducing salpingo-oophorectomy has been proposed. Currently there is enough follow-up to evaluate the results and it has been found that in patient with a STIC, after 10 years of follow-up, almost 30% develop peritoneal carcinomatosis, and if there was not STIC, 1% will develop peritoneal carcinomatosis, which is the same percentage of the risk of developing ovarian cancer. Therefore, it is clear, the risk-reducing salpingo-oophorectomy cannot prevent serous carcinomas. In addition, this operation is associated with a risk for cardiovascular disease.

The obvious question would be: if the main person proposing the theory of the origin of serous carcinoma in the fallopian tube now admits that in most cases STIC is not found, the theory cannot explain most of the facts associated with serous carcinomas, and the proposed operation does not solve the problem, but create problems, why most people still supports this theory?

There is a reason why Mark Twain said:” It is easier to fool people than to convince them that they have been fooled”.

STIC exists, but it is not the origin of ovarian serous carcinoma, it is a manifestation of the multicentricity of ovarian serous carcinoma.