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Background: Previous studies have reported the abundant expression of EBER1 in primary nasopharyngeal carcinoma (NPC) metastatic to lymph nodes and bone marrow (BM). This study was done to research the use of EBER1 in situ hybridization to detect micrometastasis in the marrow of NPC patients., Patients and Methods: A total of 41 patients who underwent BM biopsy either for routine pretherapeutic evaluation or suspected bone marrow metastasis were enrolled for study. Thirty-two patients underwent BM biopsy for routine staging examination (Group I) and 10 were examined for unexplained cytopenia, leukoerythroblastosis, disseminated intravascular coagulation, or extensive bone metastasis (Group II). The authors applied EBER1 in situ hybridization to investigate the expression of EBER1 in 42 BM specimens. Examinations were performed on paraffin embedded tissues using polymerase chain reaction-derived, digoxigenin-labeled EBER1 DNA probes., Results: Eight of 42 specimens (19%) were positive for BM metastasis. Just one (3%) had bone marrow involvement in Group I. However, seven (70%) were positive in Group II. All but one of them with bone marrow metastasis showed positive EBER1 in situ hybridization in the BM. Another patient suspected of having BM metastasis was negative for cytokeratin, but was positive for EBER1 in situ hybridization., Conclusion: Routine bone marrow study is not recommended in the staging of NPC, since only 3% of patients had BM metastasis. EBER1 in situ hybridization of marrow specimens cannot detect malignant cells earlier in NPC, but can be usefully applied to cases of equivocal marrow metastasis.

The mainstay treatment of nasopharyngeal carcinoma (NPC) is radiotherapy. Although NPC is a radiosensitive tumor, 25% of NPC patients still suffered from local relapse in Taiwan. Whether the pathologic changes induced by radiation have impact on the interpretation of suspicious recurrent NPC specimens is seldom mentioned. We retrospectively analyzed 20 irradiated NPC patients who were suspected to have local recurrence and received serial nasopharyngeal biopsies. A total of 31 nasopharyngeal tissues including 15 local recurrent specimens and 16 negative specimens were entered into this study. Compared with non-irradiated nasopharyngeal tissue, the irradiated nasopharynx showed fibrosis and areas of necrosis mixed with acute or chronic inflammation. Stroma cells were enlarged, with prominent nuclei and cytoplasm, and some bizarre cells might be confused with tumor cells. These post-irradiation effects did have an impact on histological interpretation. In this study, 2 out of 16 nasopharyngeal tissues were misdiagnosed as having no recurrent tumor by using H and E stain only. However, scattered cancer cells can be clearly visualized by using EBER1 in situ hybridization. Therefore, it is recommended that EBER1 in situ hybridization is routinely used in irradiated nasopharyngeal tissues in helping the diagnosis of recurrent NPC.

Epstein-Barr virus (EBV) has a well-established association with nasopharyngeal carcinoma (NPC), while its association with sinonasal carcinoma is still controversial. The role of EBV in sinonasal carcinoma and the potential value of EBER is situ hybridization in differentiating carcinomas originating from these anatomically neighboring regions were investigated. EBER in situ hybridization was applied to detect EBV in the specimens of surgically proved sinonasal carcinoma and the biopsies of carcinoma of the nasopharynx. EBER in situ hybridization was performed on paraffin embedded tissues by using PCR-derived, digoxigenin-labeled EBER-1 DNA probes. EBV was detected in 2 of 31 (6.5%) surgical specimens of sinonasal carcinoma, including 1 keratinizing squamous cell carcinoma and 1 adenocarcinoma. EBV was detected in all of 31 (100%) biopsies of carcinomas of the nasopharynx, including 1 keratining squamous cell carcinoma, 15 nonkeratinizing carcinomas, 14 undifferentiated carcinomas, and 1 adenocarcinoma. The present study does not support the role of EBV in the development of sinonasal carcinoma as does in carcinoma of the nasopharynx. EBER in situ hybridization is a useful adjunct for differentiating carcinomas originating from the sinonasal region and the nasopharynx.

Many anticancer treatments, including radiation therapy, have been demonstrated to work through apoptosis. The treatment of choice on nasopharyngeal carcinoma (NPC), a radiosensitive tumor, is radiotherapy. Apoptosis therefore provides a good model to predict or re-evaluate the therapeutic response in NPC. Cellular genes such as p53 and bcl-2 have been shown to be involved in apoptosis. Proliferating cell nuclear antigen (PCNA) is a useful marker for proliferating cells. This study was designed to investigate whether the expression of p53, bcl-2 and PCNA, evaluated on tumor specimens obtained at diagnosis, is indicative of the subsequent local recurrence and distant metastasis following radiation therapy. We analyzed the expression of p53, bcl-2 and PCNA by immunohistochemical methods from NPC specimens prior to radiation therapy. A total of 63 T3/T4 NPC patients including 10 patients with local relapse (Group I), 19 patients with distant metastasis (Group II), and 34 disease-free patients (Group III) were assessed. Six of the 10 (60%) group I NPC, 4 of the 19 (21.1%) group II NPC, and 13 of the 34 (38.2%) group III NPC exhibited positive p53 expression. For bcl-2 immunostaining, 8 of the 10 (80%) group I NPC, 10 of the 19 (52.6%) group II NPC, and 10 of the 34 (29.4%) group III NPC were positive. High PCNA labelling index was shown in 6 of the 10 (60%) group I NPC, 7 of the 19 (36.8%) group II NPC, and 5 of the 34 (14.7%) group III NPC. The bcl-2 and PCNA reactivity in NPC developing local recurrence after radiation therapy was significantly higher than that in the disease-free NPC (p < 0.05). These findings show that the overexpression of bcl-2 and high PCNA labelling index are probably related to local relapse in NPC patients receiving radiation therapy alone as primary treatment.

Background: We aimed to investigate the tumor biology of nasal IP and identify the biological characteristics associated with early diagnosis and malignant transformation., Materials and Methods: Lectins immunohistochemistry were performed on inverted papilloma (IP), and associated neoplasms. IP synchronized with polyp or squamous cell carcinoma (SCC) and IP metachronized with SCC were analyzed and correlated to clinical information., Results: Canavalia ensiformis (ConA) and Arachis hypogaea (PNA) with neuraminidase pretreatment (NA-PNA) showed similar staining in both the IP and SCC portions of the IP synchronized with SCC. The IP and polyp portions of an IP synchronized polyp had positive NA-PNA staining, while papilloma and polyps alone had negative staining. Strong NA-PNA staining in the IP (transformed to SCC) showed significant differences from IP., Conclusion: These biological characteristics define IP as a premalignant neoplasm. NA-PNA staining may be helpful for an early detection of IP. Strong NA-PNA staining in IP may predict malignant transformation.

Background: Although the biologic behavior of papillary cystic tumor (PCT) of the pancreas is more favorable than the adenocarcinoma, a malignant form has been reported. There has been much controversy as to the histologic evidence for malignancy. The purpose of this study is to evaluate whether the ras oncogene mutation is present in the PCT, together with hormone receptor status and DNA flow cytometry that can be used to predict tumor aggressiveness., Materials and Methods: In 6 collected cases of PCT, estrogen receptors (ER) and progesterone receptors (PR) were detected by immunohistochemical techniques, DNA ploidy and S-phase fraction (SPF) were studied by flow cytometry, and H, K, and N-ras oncogene mutation were analyzed by polymerase chain reaction (PCR)., Results: General strong positive immunostaining of PR and negative staining of ER are found in all 6 cases of PCT, including 5 adolescent girls and one 55-year-old women with areas of anaplastic transformation. Flow cytometry analysis revealed diploid DNA in all 6 cases but higher SPF in the anaplastic portion of the old one. None of the 6 cases showed H-, K-, or N-ras oncogene mutation., Conclusions: These results suggest PR status and ras oncogene mutation appear to be not useful in predicting aggressive behavior. DNA ploidy and S-phase fraction may provide useful information for prognosis, but their more precise prognostic value of PCT needs a larger number of cases to clarify.

Apoptosis or programmed cell death represents a mechanism by which tumor cells with DNA damage can be deleted. Bcl-2 and p53 gene products have both been linked to apoptosis. Bcl-2 plays a role as an inhibitor of apoptosis that may extend the viability of cells containing genetic alterations and facilitate tumor progression. Mutant p53 has a similar effect. The purpose of this study was to investigate the relationship between bcl-2 and p53 expression and to clarify their roles in apoptosis in different histological graded breast carcinomas. We analysed 101 invasive ductal carcinomas of the breast for the expression of bcl-2, p53, c-erbB-2, estrogen and progesterone receptors using immunohistochemistry. Reciprocal expression of bcl-2 and p53 was present in 71.3% of cases. The bcl-2+/p53-expression pattern was prevalent in histological grade I and II tumors (77.4% and 59.3% respectively) and rarely present in histological grade III (6.3%). Conversely, bcl-2-/p53+ expression pattern was rarely present in histological grade I and II tumors (3.2% and 11.1% respectively) and prevalent in histological grade III (50.0%). Our results also showed that Bcl-2 expression was positively correlated with ER and PR, more prevalent in pre-menopausal status, and negatively correlated with cerbB-2 expression. Bcl-2 expression was involved in tumor progression in well-differentiated tumors and mutant p53 could substitute for bcl-2 function in poorly differentiated tumors. The bcl-2/p53 expression pattern of tumors may be of value in predicting therapeutic response and prognosis. Bcl-2 expression was correlated with other well-established prognostic factors and bcl-2 could be an estrogen-related protein.

Established cancer cell lines with distinct characteristics are valuable in many aspects of in vitro study pertaining to tumor biology, as well as the possible geographic significance. Two long-term cell lines, BFTC905 and BFTC909, were established from primary transitional cell carcinomas (TCC) of patients from a blackfoot disease endemic area in Taiwan, where the prevalence and standard mortality rates of this cancer are unusually high. BFTC905 derived from a grade III TCC of urinary bladder has an epitheloid morphology, and BFTC909 derived from the sarcomatoid component of a grade III TCC of renal pelvis exhibits a fibroblastic growth pattern. They share similar morphological and immunocytochemical characteristics with the tumors of origin, have multiple chromosomal aberrations, and are tumorigenic in nude mice. BFTC905 reveals a unique homogeneously staining region at 11q13, the amplification of which has been detected in 20% of transitional cell carcinoma. In addition to the rarity of renal pelvic origin, the vimentin expression associated with an aggressive clinical behavior and a relatively high tumorigenicity as demonstrated by BFTC909 cells has also rarely been mentioned in TCC cell lines, but has been well documented in vivo and in vitro in renal cell carcinoma and breast cancer.