Jens Sandros

Cytogenetic and molecular observations in human and experimental salivary gland tumors

The chromosomal banding patterns in 189 benign and malignant salivary gland tumors are reviewed. For comparison, karyotypic data from a recent series of polyoma virus-induced salivary gland tumors in the mouse are discussed. Special interest is focused on the relationships between the highly specific patterns of translocations and deletions in these tumors and different genes involved in neoplasia, in particular oncogenes, and tumor suppressor genes.

6q- and loss of the Y chromosome—Two common deviations in malignant human salivary gland tumors

Nine cases of malignant human salivary gland tumors cultured in vitro were subjected to detailed cytogenetic analysis with G-banding. Together with observations from three earlier published cases, the results of 12 cases were surveyed: five adenoid cystic carcinomas, three acinic cell tumors, three adenocarcinomas, and one mucoepidermoid carcinoma. All tumors had stemlines in the diploid-near-diploid mode. The most consistent changes among the adenoid cystic carcinomas were stem lines and/or variant cells with anomalies affecting the terminal part of 6q (i.e., 6q 16-25). Deviations affecting the Y chromosome (losses) and, to a lesser extent, #6 (structural changes) and #8 (gains) characterized the early karyotypic evolution in acinic cell tumors. Two of the three analyzed adenocarcinomas showed stemlines or variant cells with loss of gonosomes. The karyotypic features of the different tumor types, including primary changes, evolutionary characteristics, and progressional pathways, are discussed. The cytogenetic relationships between benign and malignant salivary gland tumors also will be considered.

Significance of the choice of tissue culture technique on the chromosomal patterns in human mixed salivary gland tumors

Cytogenetic observations by banding methods in 56 new cases of human benign pleomorphic adenomas are reported. Thirty of the cases (series I) were studied in preparations from primary cultures established from cells growing out from mechanically dispersed tumor pieces. The remaining 26 cases (series II) were analyzed in preparations from primary cultures established from enzymatically pretreated material. The use of the latter method resulted in a decrease in the frequency of cases with a normal stemline from about 53% to about 19%. However, the general characteristics of the aberrations observed in abnormal stemlines in both series agreed well. The minor differences observed consisted of a higher frequency of recurrent t(3;8)(p21;q12) in series II and, in the same series, fewer cases showing an involvement of 8q or 12q. The present results emphasize the importance of molecular studies of, in particular, the regions 8q12, 12q13-15, and 3p21.

Partial 6q deletion in a human salivary gland adenocarcinoma

G-banding analysis was performed on a cultured human salivary gland adenocarcinoma. Clonal chromosome abnormalities consisted of a 6q- marker and loss of the Y chromosome. The 6q- marker had resulted from a long arm interstitial deletion, del(6)(q22q24). The present results, together with our previous findings of 6q deletions in other types of salivary gland tumors, indicate that deletions of 6q are characteristic for the karyotypic evolution of all major types of malignant salivary gland tumors. A common pathogenetic mechanism for these tumors might well be loss of a tumor suppressor gene located on 6q.

Expression of p21RAS in odontogenic tumors

Using an immunohistochemical assay 10 benign odontogenic tumors were evaluated for expression of the HRAS‐ and KRAS‐encoded gene products p21RAS. Overexpression of p21RAS was found in ameloblastomas, ameloblastic fibromas and odontogenic myxomas compared with normal human developing teeth. The highest expression was noted in a recurrent plexiform ameloblastoma in which almost 100% of the tumor cells were brightly reactive. In general, p21RAS was preferentially expressed in ectodermal cells of odontogenic tumors, consistent with the findings in the tooth germs. The significance of p21RAS expression is considered in relation to the biological behavior of ameloblastomas.

Prevotella bivia can invade human cervix epithelial (HeLa) cells

Prevotella bivia has been associated with female upper genital tract infections and an increased risk of preterm delivery. In this study, the adherence and invasion capacity of P. bivia was investigated using a cervix epithelial cell line. P. bivia was furthermore analysed for its ability to evoke a proinflammatory cytokine response in epithelial cells. The invasion capacity, defined as the number of bacteria recovered from lysed HeLa cells infected with P. bivia, varied considerably among five strains, all of which were isolates from women with bacterial vaginosis. One P. bivia strain (P47) gave rise to an approximately 120‐fold higher number of intracellular bacteria (7×103 bacteria per 1×105 cells) compared with the least invasive strain. Three strains expressed an intermediate or low invasiveness, showing an approximately 3‐ to 40‐fold higher number of intracellular bacteria per 1×105 cells compared with the least invasive strain. The intracellular localization of P47 in phagosome‐like vesicles was confirmed by transmission electron microscopy. All P. bivia strains adhered to HeLa cells to the same extent (range 14–22 bacteria per cell) as analysed by interference microscopy. No correlation was found between adhesion and invasion capacity of the strains. Furthermore, no fimbriae‐like structures were observed on P47 detected by scanning electron microscopy or negative staining. Analysis of TNF‐α, IL‐1α, IL‐6, IL‐8, and IL‐18 in P. bivia‐stimulated HeLa cells showed low levels of only IL‐6 and IL‐8 for the most invasive P. bivia strain P47. Thus, the induction of IL‐6 or IL‐8 secretion appeared to be associated with invasion capacity. This work provides evidence that some P. bivia isolates can invade human cervix epithelial. Thus, a strong capacity for invasion and a weak proinflammatory cytokine‐inducing capacity in P. bivia are suggested to be virulence factors in establishing a low‐grade upper genital tract infection.