Clinically Aggressive Pseudomyxoma Peritonei: A Variant of a Histologically Indolent Process

FAHEEZ MOHAMED, MBChB, MRCS,1 SUE GETHING, MT (ASCP),2 MOUTAZ HAIBA, MD,2 ERWIN A. BRUN, MD,2AND PAUL H. SUGARBAKER, MD, FACS, FRCS1*

1The Washington Cancer Institute, Washington Hospital Center, Washington, District of Columbia2Department of Pathology, Washington Hospital Center, Washington, District of Columbia
 
Journal of Surgical Oncology 2004; 86:10–15
 

It is widely believed that the DPAM variant of PMP is slow progressing, has a more favorable survival, and responds better to treatment as opposed to the more malignant variants. Unfortunately there are numerous cases where patients with DPAM succumb to an invasive, fast progressing disease.

This study tries to investigate the reason why some DPAM show aggressive behavior. The study tested 11 patients with this form of invasive, recurrent, aggressive DPAM and chose 22 patients as a control group with a history of DPAM but no evidence of disease at the time of study. Slides of cancerous tissues were processed from all patients, and were stained with anti bodies to mucin antigens MUC1 and MUC2. Mucins are glycoproteins; a carbohydrate molecule with a protein backbone.

In most types of cancer, mucin production has been reported, of all the mucins, MUC1 and MUC2 have been the most studied and characterized. In an effort to distinguish the regular DPAM from the more invasive DPAM, the researchers decided to investigate the expression of MUC1 and MUC2 antigen in these tumors. The results showed all 11 patients in the study with an upregulation of MUC2, and 7 had an upregulation of MUC1 .The control group an upregulation of MUC2 in 21 out of 22 patients, and upregulation of MUC1 in 12 out of 22 patients.

According to the results, MUC2 overexpression supports a primary tumor of appendiceal origins rather than ovarian origins. The study also maintained that although MUC2 was overexpressed, it was not correlated to aggressive behavior of abnormal DPAM as it was expressed in high levels in both groups. Alternate reasons were presented for the unusual course of invasive DPAM. One reason was an error in the diagnosis of classification of DPAM. In a different study, after repeated use of cytoreductive surgeries and HIPEC treatment 7 out of 19 patients had a transition from a less aggressive form to a more aggressive form. The 11 patients in this study however, did not show progression to malignant forms of PMP. Perhaps, it is possible that during prior extensive surgery, transfer of surface tumor was converted to a deeply embedded one as a result of surgical dissection. In addition, some of tumor cells may not respond well to HIPEC treatments using mitomycin-C and 5-flourouracil therapeutic agents. In this case, those resistant tumors may then implant themselves on tissues surfaces of nearby organs thus prompting an invasive process.

Unfortunately, the study did not think MUC1 and MUC2 should be used as prognostic factors as they do not appear to be particularly useful in predicting the pathogenesis of aggressive forms of DPAM. It does however conclude that more investigations at a molecular and genetic level may be helpful in identifying the variant forms of DPAM, or better yet, may provide a more comprehensive pathological classification.