​The Prognostic Effect of Immune Cell Infiltration Depends on Molecular Subtype in Endometrioid Ovarian Carcinomas
Heinze, Cairns, et al. Clin Cancer Res. 2023 Sep;9(17): 3471–3483.
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In most people, the immune system recognizes and attaches foreign substances like bacteria and viruses. When an individual is affected by cancer, the immune system has trouble identifying these unhealthy cells since they are our own cells with some of the same safety mechanisms to prevent immune system attack. People with cancer who have a greater number of immune cells in and around cancer typically have better outcomes and a stronger anti-cancer response, but the types of immune cells that are present and how they interact with cancer can have a large effect.
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For endometrioid ovarian cancer, we found that we could divide cancers into three groups: those with a lot of immune cells, those with almost none, and those with only specific subsets of immune cells. The first two groups seem to have excellent outcomes but individuals in the last groups did not do as well.
We found that this poor-outcome group tended to have immune cells that were unable to react to the cancers. This group was also missing B-cell, which we believe may be necessary to re-activate and direct anti-tumor action. While additional work on this type of cancer is needed, our finding suggested that some endometrioid ovarian cancers might benefit from new drugs, known as immune checkpoint inhibitors, that act to remove inhibitory signals from immune cells.
summary: M.S.A; K.H.; H.O.A
Heinze, Nazeran, et al. J Pathol. 2022 Apr;256(4):388-401.​
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In endometriosis-associated ovarian cancer, a specific gene called ARID1A is often lost due to mutation. There are conflicting reports on how losing this gene affects the behaviour of these cancers. To better understand the impact of ARID1A loss in endometriosis-associated ovarian carcinomas, we studied the outcomes and other characteristics of a large group of individuals with either endometrioid (ENOC) or clear cell (CCOC) ovarian carcinomas.
Contrary to smaller previous studies, we found that the loss of the ARID1A gene did not affect patient outcomes. In CCOC, the loss of ARID1A was not linked to the age of cancer onset, the spread of the disease, or the immune system’s response to these cancers. However, in ENOC, patients with ARID1A loss tended to be younger and were more likely to trigger an immune response to their cancer. Additionally, we discovered that a second mutation, which impairs the DNA’s ability to repair errors, often leads to the loss of ARID1A in ENOC. This increase in mutations also seemed to attract a stronger immune response to the tumours.
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summary: H.O.A.; M.S.A.
Yong, Bedaiwy, et al. Best Pract Res Clin Obstet Gynaecol. 2021 Mar;71:2-13.​​​
Bowel endometriosis occurs when tissue from the uterus grows on the outer surface of the intestine or rectum. The formation of bowel endometriosis, like other endometriosis, is though to result from cells escaping the uterus during menstruation and ending up in the peritoneal cavity instead of being shed externally. The uterine cells become trapped and in some cases are able to change how they grow to stay alive in this new environment. These changes alter how uterine cells interact with each other and their surrounding, resulting in inflammatory reactions, invasion, adhesion to multiple surfaces, and recruitment of new blood vessels and nerve fibres. Many of these features are responsible for painful symptoms. Questions remain on mechanisms that enable uterine cells to survive where they are not normally found.
This review presents our current knowledge on bowel endometriosis, clinical and surgical treatment challenges, and some potential mechanism that contribute to its formation and symptoms. Mechanisms may be influenced by origin of cells, microbes (bacteria or yeast) and mutations. In particular, our research has described DNA mutations in endometriosis cells. These non-inherited mutations, similar to those found in cancers, are present in bowel endometriosis cells and, similar to cancers, may impact how these cells interact with and invade tissues.
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summary: P.S.P.; H.O.A., M.S.A.
Lac, Verhoef, et al. Hum Reprod. 2019 Jan;34(1): 69–78.
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Historically considered a benign gynecological disease, endometriosis shares many characteristics with cancer. This study was one of the first to compare the genetics of naturally occurring endometriosis (deep endometriosis; DE) to endometriosis that occurs from accidental manual movement of endometrial cells – such as during a surgery (incisional endometriosis; IE). Incisional endometriosis (IE) can occur in or around a surgical scar due to the unintentional displacement, most commonly following a C-section where the uterus is cut into. Deep infiltrating endometriosis (DE), on the other hand, occurs spontaneously when endometrial tissues invades organs or tissues.
This study found that ~27.5% of IE cases and 36.1% of DE cases carry non-inherited, cancer-associated mutations – despite the risk of cancer for either condition being exceptionally low. The frequency of mutations is similar between surgically caused and naturally occurring endometriosis, with only non-significant variation in specific mutations. This may reflect a similar mechanism by which mutations are acquired in either type of endometriosis and may support a common origin of disease: displaced endometrial cells.
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summary: H.O.A., M.S.A.