The authors have declared that no competing interests exist.
An association between the measles virus and Hodgkin lymphoma has been disclosed by our laboratory in Beer-Sheva, starting in 2003. We question the refutation of our study and the absence of interest among experts.
It was based on immunohistochemistry with commercial, as well as experimental anti-measles antibodies. It relied also on RT-PCR and
At this stage (2004), the link between the virus and the lymphoma was essentially descriptive. The first and last response to our challenge appeared in 2007, in the form of doublet articles, in the same issue of a major cancer journal. The two European research groups responding, rejected categorically our findings by proposing different arguments.
As reservations to these reactions became soon apparent, a series of papers from our laboratory were published. These articles concerned the evidence of a relationship between the measles virus and additional categories of cancers. Different malignancies in which this virus was not expressed at all, were also described. A further study suggested a mechanism by which the measles virus may activate lymphomagenesis in classic Hodgkin lymphoma. To our dismay, and in spite of repeated calls to verify the various results, no further response was obtained from international experts.
A hypothesis has been presented in 2004, supporting a role in cancer, for the measles virus (MV), a virus which had not been considered to date as carcinogenic
In this paper, we present an overview of our endeavour for the recognition of a common virus, as the heart of malignancies, to which it had not been associated until now. The thesis further suggests a role for the virus in oncomodulation, in a manner which evokes the controversial effect of the cytomegalovirus in glioblastoma
However, the main issue is that the hypothesis has been rejected by two major groups of scientists in cooperation
A commentary is presented.
In 2004, we revealed a link between classic Hodgkin lymphoma (cHL) and the measles virus (MV), using immunophenotyping and several anti-MV antibodies. Of 154 cHL biopsies, 82 were positive for MV antigens (54%)
The expression of the MV antigens was evaluated in a clinicopathological association. Positive expression of MV favored female patients (p=0.036), nodular sclerosis cHL (p=0.0013) and early stages of the lymphoma. However, overall, MV-positive expression seemed to be related to a worse prognosis
Maggio et al, from Essen, Germany rejected our findings. They were highly selective in their study, and chose 18 of their original 44 snap-frozen cHL tissues, as well as 7 of our 22 cases. The RNAs had to be of a very high quality and the HRS cells chosen had a near perfect morphology. These cells were obtained in single cell microdissection
Wilson et al, from Glasgow, UK, refuted also our results
The striking selection employed in Germany, as mentioned above, may have led a bias in the analysis. Our use of a non-selected cohort of cHL patients had pointed out at a low-abundance of MV-RNA, which may be due in part to a long shelf time of the deep-frozen tissues, but also in part to the often numerous ribonuclease-rich eosinophils content in cHL. Thus GAPDH might not be an adequate housekeeping gene in these experiments
On the other hand, a large part of the Scottish cohort had suffered from acute measles, mainly as children. This is not in agreement with the concept of the late host response model, which suggests that these patients might be protected from the development of cHL
Moreover, using the clone 49-21 (anti-MV-antibody), but this once from Argene-Biosoft, France (#11-045), more than half of our cases were positive for the MV antigen
Seventy-two percent of our 49 endometrial carcinoma cases were positive for MV antigens in the tumor cells. Using
In the 65 non-small cell carcinomas of lung studied, 54 were positive for MV proteins
With regard to the 131 cases of invasive ductal carcinomas examined, 64% were positive for MV antigens
In contrast, the non-Hodgkin lymphomas studied did not express MV antigens, except for the ALK-positive anaplastic large cell lymphoma. Of equally negative MV expression, were seminomas, glioblastomas and mesotheliomas
A second look at the apoptotic status in cHL (apoptotic index) disclosed that, as expected, apoptosis was inhibited in this lymphoma, but that the hindrance was found in 55% of the 217 cases studied only. It is proposed therefore that the MV might regulate cHL via modulation of apoptosis in the tumor cells
A role for the MV has been hypothesized by us in cHL, role which
The situation today may lean in favour of our thesis, as we have carried on with our research and are still publishing in this domain. However, due to the seniority of the retractors, we still have serious doubts regarding the validity of our data. This is why, we call, once again for the international scientific community reappraisal of our work, as well as for attempts at the reproduction of our research by other investigators.
We are searching for new means of bringing our work to the attention of the experts.
We thank kibbutz Sde-Boker for their support.