Diagnostic and prognostic evaluation of phenotypic markers TRAF1, MUM1, BCL2 and CD15 in cutaneous CD30-positive lymphoproliferative disorders.

BACKGROUND: CD30 is expressed in various types of cutaneous lymphomas, including lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (C-ALCL), some cases of mycosis fungoides showing large cell transformation (MF-TR) and skin localizations of systemic anaplastic lymphoma kinase (ALK)-positive or ALK-negative ALCL. Differentiation between these entities is often not possible on the basis of histology alone, but several markers, including TRAF1, MUM1 and BCL2, have been reported to provide additional diagnostic information. OBJECTIVE: To evaluate the diagnostic and prognostic significance of these markers in a large group of cutaneous CD30-positive lymphoproliferations. METHODS: An immunohistochemical study on the expression of TRAF1, MUM1, BCL2 and CD15 was performed on skin biopsies from 28 patients with C-ALCL, 39 patients with LyP, 11 patients with CD30-positive MF-TR, two with ALK-positive ALCL and six with ALK-negative ALCL. In addition, the prognostic significance of these markers was evaluated. RESULTS: TRAF1 was expressed in roughly 70-80% and MUM1 was expressed in 70-100% of all the groups of cutaneous CD30-positive lymphoproliferations. Highest levels of BCL2 were expressed in MF-TR (73%), in contrast to 21% in C-ALCL and 36% in LyP. Highest levels of CD15 were expressed in C-ALCL (43%), compared with 18% in LyP and 9% in MF-TR. A relationship with survival was not clear. CONCLUSIONS: The results of the present study suggest that TRAF1, MUM1, BCL2 and CD15 cannot be considered as useful diagnostic or prognostic marker in cutaneous CD30-positive lymphoproliferations. Differentiation between these different conditions should be based on a combination of clinical, histological and immunophenotypical criteria.

Bone marrow examination has limited value in the staging of patients with an anaplastic large cell lymphoma first presenting in the skin. Retrospective analysis of 107 patients.

BACKGROUND: According to criteria of the World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas a diagnosis of primary cutaneous CD30-positive anaplastic large cell lymphoma (C-ALCL) should be made only when systemic localizations have been excluded by adequate staging procedures, including a bone marrow biopsy. It has recently been questioned whether or not bone marrow examination should be performed routinely in indolent cutaneous lymphomas such as C-ALCL. Studies addressing this issue have never been performed. OBJECTIVES: To determine the incidence of bone marrow involvement in patients with an ALCL first presenting in the skin to find out if the current policy to advise bone marrow examination should be maintained or whether a bone marrow biopsy should be performed only in selected cases. METHODS: All patients presenting with skin lesions with histological and immunophenotypical features of an ALCL were retrieved from the database of the Dutch Cutaneous Lymphoma Group. Patients with a history of systemic ALCL and patients without bone marrow examination were excluded from the study. The final study group included 107 patients with an ALCL first presenting in the skin, who had been staged completely. RESULTS: Staging procedures showed the presence of extracutaneous disease in 20 patients, but bone marrow involvement was not detected in any of the 107 patients. Moreover, only one patient developed bone marrow involvement during follow up (median follow-up period 69 months). CONCLUSIONS: Bone marrow examination has limited value in the staging of patients with an ALCL first presenting in the skin, and should be performed only in selected cases.

Liposomal enhancement of the antitumor activity of conditionally replication-competent adenoviral plasmids.

Many human tumors have a functional deficiency in p53. Numerous studies have taken advantage of this phenomenon to use a conditionally replication-competent adenovirus (Ad dl1520) that will grow in and lyse tumor cells while sparing normal tissues. However, success has been limited, in part due to difficulties in reaching a sufficiently high proportion of tumor cells. Preexisting or developing immune responses directed toward viral proteins further decrease the efficacy of the approach. We have developed a liposome-encapsulated conditionally replication-competent plasmid based on the dl1520 virus. Like the parent virus, this plasmid generates infectious particles following transfection of p53-defective, but not p53-wild-type tumor cells, but unlike the parent virus it is able to infect CAR-negative tumor cells. The antitumor efficacy of this infectious plasmid was demonstrated in mice with xenografted human tumors, in which it was active after both local and intravenous administration for subcutaneous tumors and following intravenous administration for disseminated malignancy. Activity was retained systemically, even in the presence of neutralizing antibody. Such liposomally encapsulated conditionally replication-competent plasmids may complement the use of conventional viral particles, particularly in settings in which liver uptake of adenoviral vector is undesirable or there are problematic inhibitory effects from humoral immune responses.

Field and numerical analysis of in-situ air sparging: a case study.

An in-situ air sparging operation was used to remediate the sandy subsurface soils and shallow groundwater under a drum storage site near Chicago, IL, where either periodic or random spillage of a light non-aqueous phase liquid (LNAPL) occurred between 1980 and 1987. Both field measurements and model simulations using commercially available computer software suggested that microbial degradation was the most significant contributor to the removal of contaminant mass. Toluene, ethylbenzene and total xylenes (TEX), which were of major concern with regards to reaching clean-up criteria at the site, were observed to decline by 88% in concentration. Furthermore, up to 97% of the total mass removed through microbial degradation consisted of TEX. Of the total contaminant spill, up to 23% of initial organic chemical mass was removed through microbial degradation compared to less than 6% by physical stripping. Greater loss to microbial degradation is most likely attributed to the relatively low air injection rate used during the course of the air sparging remediation. Evaluation of air sparging at the site using model simulations supported this analysis by estimating 140 and 620 kg of total contaminant mass being removed through volatilization and biodegradation, respectively. An evaluation of several system design parameters using model simulations suggested that only the type of sparging operation (i.e. pulsed or continuous) was significant in terms of total contaminant removal time, while both the sparging operation and air injection rate were significant in terms of removal of a critical species, total xylenes.

Developmental changes of adenocarcinoma-associated antigen.

The occurrence and serum concentrations of adenocarcinoma-associated antigen (ACAA) were studied during the fetal period of life, in newborns and in their mothers. The mean concentrations were significantly higher in fetal, newborn and maternal sera when compared with the mean concentration of ACAA in healthy, nonpregnant adults. Thus, ACAA appears to show fetospecific features as is known for other oncofetal proteins. ACAA should be recognized not only as a potential tumor marker, but also as a normal protein constituent of human serum.

Ontogeny of pancreatic oncofetal antigen.

Serum concentration of pancreatic oncofetal antigen (POA) was determined in human fetuses, newborns and pregnant women. The mean fetal concentration of POA (mean = 5.27 micrograms/ml) changed very little with gestational age. Also, only a weak correlation was found between POA concentration of newborns (mean = 5.15 micrograms/ml) and their birth weight. It appears that between the 19th and 40th weeks of gestation POA exhibits no fetospecific features, i.e. POA concentration did not exceed significantly the concentration of nonpregnant adults (mean = 6.10 micrograms/ml). A number of pathophysiological variables was correlated with POA concentrations of newborns. The most striking statistical differences were found between American black and white newborns and adults; the mean concentration of POA in sera of black full-term newborns was 5.38 micrograms/ml as compared to white newborns, where the mean concentration was 3.58 micrograms/ml. Similarly, black mothers had a mean concentration (mean = 12.21 micrograms/ml) significantly greater than white mothers (mean = 5.62 micrograms/ml).