The relationship with human papilloma virus DNA in cervical adenocarcinoma

Recently, cervical adenocarcinoma has been increasing especially among young women and account for 10-20% of cervical cancer. However, the detection rate of HPV-DNA was 35-85% and lower than that of squamous cell carcinoma. Furthermore, the relationship with HPV in cervical adenocarcinoma was not much investigated in Japan, so we studied HPV status in cervical adenocarcinoma by in situ PCR method using biotin-labeled DNA probes, because in situ PCR method possesses the advantages of both PCR and in situ hybridization in being highly sensitive and enabling visualization of the cellular localization of the DNA. HPV infection was analyzed in 60 cervical adenocarcinomas, including 1 adenocarcinoma in situ and 15 adenosquamous carcinomas. HPV-DNA was detected in 47 of all 60 cases(78%): 35 of 45(78%) in adenocarcinomas and 12 of 15(80%) in adenosquamous carcinomas. No significant correlation was found between the HPV-DNA detection rate and histological subtypes of adenocarcinoma. In conclusion, cervical adenocarcinoma demonstrates a high prevalence of HPV-DNA as well as other previous studies. Therefore, HPV infection plays a very important role in not only squamous cell carcinoma but also adenocarcinoma in uterine cervix.     

Prevalence of human papillomavirus DNA in various histological subtypes of cervical adenocarcinoma: a population-based study.

The role of human papilloma virus (HPV) infection in the development of cervical carcinoma is well established, however, the prevalence of HPV DNA in cervical adenocarcinoma varies from study to study. It appears to be caused by a number of factors, one of which is that cervical adenocarcinomas comprise a heterogeneous group of multiple subtypes. To clarify the impact of HPV infection on the development of cervical adenocarcinoma with diverse histological subtypes, we performed a population-based study in Korean women from 15 different institutes for the status of HPV infection in adenocarcinoma of uterine cervix. A total of 432 cervical adenocarcinomas from 1997 to 2001 were reviewed and classified according to the modified WHO classification. For 135 cases, HPV typing was performed with HPV DNA chip (82 cases) and PCR HPV typing (53 cases), using formalin-fixed, paraffin-embedded archival tissue. The overall prevalence of HPV infection in cervical adenocarcinoma was 90%. The infection of HPV 16 and/or HPV 18 accounted for 78% of HPV-positive adenocarcinomas. Multiple HPV types were found in 13% of the cases. The HPV DNA was rarely detected in minimal deviation adenocarcinoma. Interestingly, HPV 16 was a predominant type in endometrioid and villoglandular types, whereas HPV 16 and HPV 18 were detected with equal prevalence in other subtypes. In conclusion, HPV infection, mostly HPV 16 and HPV 18, is highly associated with most of the cervical adenocarcinomas, whereas endometrioid and villoglandular type have a different pattern of HPV infection status. Minimal deviation adenocarcinoma does not seem to be related with HPV infection.     

Human papillomavirus infection and invasive cervical neoplasia: a study of prevalence and morphology

The prevalence of human papillomavirus (HPV) DNA sequences in 45 cervical cancer biopsies was examined with the hot-start polymerase chain reaction (PCR), employing HPV consensus primers from the L1 region. The cases comprised 38 squamous cell carcinomas, three adenosquamous carcinomas, and four adenocarcinomas. PCR products were typed with single-strand conformation polymorphism (SSCP) and the HPV types detected were correlated with tumour type. Forty-three biopsies were HPV-positive, HPV16 being the most prevalent type. HPV18/33/45/58 were also detected, but no low-risk or multiple types. Keratinizing squamous cell carcinoma was invariably associated with HPV16 and adenosquamous carcinoma and adenocarcinoma with HPVs 18/45. Non-keratinizing squamous cell carcinomas harboured all five detected types. Our data corroborate the view that malignant cervical tumours are almost invariably associated with high-risk HPV and that certain malignant cervical tumour phenotypes correlate with specific HPV types. © 1997 John Wiley & Sons, Ltd.     

Multiple HPV genotypes in cervical carcinomas: improved DNA detection and typing in archival tissues.

BACKGROUND: Human papillomaviruses (HPV) have been considered to be the necessary and central agents of cervical carcinoma. OBJECTIVE: The aim of this study was to determine the prevalence and genotypes of HPV in archival cervical carcinomas. STUDY DESIGN: The study included 152 paraffin-embedded, formaldehyde-fixed cervical carcinoma specimens. To improve the detection and typing of HPV in archival tissues, we conducted a comprehensive study in which, polymerase chain reaction (PCR)-based methods using E7 type-specific (TS) and L1 modified general primers (MY11/GP6+ and GP5+/GP6+) were employed. RESULTS: Overall HPV prevalence was 98% in the cervical carcinomas. HPV 16 was detected in 66% of the tumors, HPV 18 in 22%, HPV 31 in 13%, HPV 33 in 9%, and HPV 58 in 9%. Notably, multiple HPV types were present in 44 (28.9%) of the 152 cervical carcinomas. The most common co-infections were HPV types 16/18 (12 cases), followed by HPV types 16/31 (7 cases). Additionally, HPV 18 was more frequent in adenocarcinomas and adenosquamous carcinomas (86%) than in squamous cell carcinomas (15.8%) (P = 0.0002). CONCLUSIONS: The combination of L1 general primers and E7 type-specific primers can be of use in detecting HPV DNA in archival tissues. The present study showed a high frequency of multiple HPV infections in cervical carcinomas. Hence, relevant HPV typing information in cervical carcinoma is very important for further HPV vaccine design and application.     

In situ DNA hybridization of cervical small cell carcinoma and adenocarcinoma using biotin-labeled human Papillomavirus probes.

A preferential association of human Papillomavirus (HPV) type 18 with cervical small cell carcinoma and adenocarcinoma has been identified by in situ and blot hybridization analysis using radionucleotide-labeled DNA and RNA probes. We attempted to detect HPV DNA in nine cases each of invasive cervical small cell carcinoma and adenocarcinoma using biotin-labeled probes to HPV types 6/11, 16/31/33/35, and 18 with a peroxidase-conjugated streptavidin detection system. HPV type 18 DNA was detected within four of nine small cell carcinomas and one of nine adenocarcinomas. HPV types 16/31/33/35 were detected in one additional case of cervical adenocarcinoma. All HPV-positive small cell and glandular tumors showed a distinctive, punctate, often juxtanucleolar pattern of nuclear staining which involved the majority of carcinoma cells throughout each neoplasm. This pattern of HPV DNA labeling has not been observed in any of the HPV-positive typical squamous carcinomas or condylomas hybridized at our institution. It is possible that punctate nuclear HPV DNA staining is a marker of viral integration into the host cell genome. We conclude that in situ DNA hybridization with biotinylated probes, although less sensitive than detection of virally transcribed RNA, still allows detection of relatively low copy numbers of HPV DNA in cervical small cell carcinomas and adenocarcinomas. Furthermore, the spatial precision of biotinylated probes may provide morphological information not obtainable using radionucleotide-labeled probes.     

Human papillomaviruses and cervical cancer: analysis of histopathologic features associated with different viral types

The histopathologic features of 41 cervical carcinomas were correlated with the presence of human papillomavirus (HPV). Southern blots of DNA extracted from the tumors were hybridized with 32P-labeled type specific probes for HPV 6, 11, 16, 18, and 31. HPV was found in 26/41 (63%) of the tumors. The HPV types were: HPV 16 in 17 tumors (41%), HPV 18 in six tumors (15%) and HPV 31 in two tumors (5%). No tumor hybridized to either HPV 6 or HPV 11. HPV was identified in all histologic subtypes of cervical carcinoma; however, different HPV types were associated with specific histologic features. HPV 18 was identified in four of eight adenocarcinomas, while HPV 16 was found in only one. HPV 16 was most strongly associated with the keratinizing tumors. It was found in 10/13 (77%) of the large cell keratinizing (LCK) and in only 4/16 (25%) of the large cell nonkeratinizing cervical carcinomas (LCNK). A mucoepidermoid with extensive keratinization and pearl formation also contained HPV 16. One of three additional adenosquamous carcinomas had HPV 31, as did one LCNK tumor. In one LCK tumor, a HPV was identified that hybridized to both HPV 16 and 18. The LCNK group contained the highest percentage of tumors in which no papillomavirus DNA was identified (9/16 lacked HPV DNA). No papillomavirus was detected in six tumors from other sites or in five cervical specimens with no histologic evidence of HPV infection. These data indicate that HPV is involved in all major histologic types of cervical carcinoma, and suggest that the different HPV types transform slightly different cell populations, or that transformation by HPV 18 tends to induce adeno-differentiation while HPV 16 leads to squamous maturation.     

Detection of human papillomavirus DNA in invasive cervical cancers by the polymerase chain reaction and its clinical significance.

In order to detect human papillomavirus (HPV) DNA in invasive cervical cancers, three different polymerase chain reactions to amplify different subgenomic fragments of HPV DNA were carried out on DNA extracted from 93 formalin-fixed and paraffin-embedded tumor tissues. This study detected HPV DNA in 54 cases (58.1%), which broke down to HPV 16 in 39 (41.9%) cases, HPV 18 in six (6.4%), HPV 52 in three, HPV 33 in one and unclassified HPV type in the remainder. Histopathologically, squamous cell carcinomas frequently contained HPV 16, whereas, HPV 18 was present in adenocarcinoma, adenosquamous cell carcinoma and small cell carcinoma of the cervix. Clinicopathological study revealed that HPV 16 and 18 DNA found were more frequently than other HPV subtypes in premenopausal patients. Moreover, HPV 18 DNA-positive cancers had a relatively high recurrence rate. These results indicate that cervical cancers might be clinically influenced by the difference in subtypes of the infecting HPV.     

Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis

To clarify the role of human papillomavirus (HPV) in penile cancer we evaluated the prevalence of HPV DNA in different histological subtypes of penile carcinoma, dysplasia, and condyloma using a novel, sensitive SPF10 HPV polymerase chain reaction assay and a novel genotyping line probe assay, allowing simultaneous identification of 25 different HPV types. Formalin-fixed, paraffin-embedded tissue samples were collected from the United States and Paraguay. HPV DNA was detected in 42% cases of penile carcinoma, 90% cases of dysplasia, and 100% cases of condyloma. There were significant differences in HPV prevalence in different histological cancer subtypes. Although keratinizing squamous cell carcinoma and verrucous carcinoma were positive for HPV DNA in only 34.9 and 33.3% of cases, respectively, HPV DNA was detected in 80% of basaloid and 100% of warty tumor subtypes. There was no significant difference in HPV prevalence between cases from Paraguay and the United States. In conclusion, the overall prevalence of HPV DNA in penile carcinoma (42%) is lower than that in cervical carcinoma (approximately 100%) and similar to vulvar carcinoma (approximately 50%). In addition, specific histological subtypes of penile cancer--basaloid and warty--are consistently associated with HPV, however, only a subset of keratinizing and verrucous penile carcinomas is positive for HPV DNA, and thus these two tumor groups seem to develop along different pathogenetic pathways.     

Age-related alteration in the association of microsatellite instability with absent hMLH1 expression and histological types of colorectal carcinoma

Microsatellite instability (MSI) is present in approximately 15-20% of sporadic colorectal cancers. However, despite the increased prevalence of absent hMLH1 expression and MSI in colorectal cancer in the elderly, few attempts have been made to define it in detail. The aim of the present paper was to correlate age-related alterations in absent hMLH1 expression and MSI with various histological types of colorectal carcinoma. hMLH1 expression and microsatellite status were studied in 184 colorectal carcinomas (49 well-differentiated, 49 moderately differentiated, 49 poorly differentiated adenocarcinomas, and 37 mucinous carcinomas). The prevalence of absent hMLH1 expression was higher in poorly differentiated adenocarcinoma (63%) and mucinous carcinoma (43%) than in well- (8%) and moderately (12%) differentiated adenocarcinomas. MSI was found more frequently in poorly differentiated adenocarcinoma (69%) and mucinous carcinoma (41%) than in well- and moderately differentiated adenocarcinomas (8% and 6%, respectively). Age-related differences in absent hMLH1 expression and MSI were found only in poorly differentiated adenocarcinoma, in which the prevalence of medullary-type carcinoma increased with advancing age. These results indicate that an age-related increase of medullary-type tumors in poorly differentiated adenocarcinoma may play an important role in the increase of absent hMLH1 expression and MSI in colorectal carcinoma.     

The value of HPV DNA typing in the distinction between adenocarcinoma of endocervical and endometrial origin

AIMS: Distinguishing between adenocarcinomas of endocervical and endometrial origin histologically can be difficult, particularly in small biopsies. Most endocervical adenocarcinomas contain human papillomavirus (HPV) deoxyribonucleic acid (DNA) of 'high-risk' (HR) types, whereas this has not been consistently demonstrated in endometrial adenocarcinomas. The aim of this study was to determine whether HPV DNA testing could aid in this differential diagnosis. METHODS: The frequency of HPV DNA in paraffin-embedded tissue samples from 50 endocervical and 50 endometrial adenocarcinomas was investigated using polymerase chain reaction (PCR) amplification techniques involving (i) a screening HPV test followed by HPV DNA sequencing, and (ii) a test designed to detect HR genotypes 16, 18, 31, 33, 35, 45 and 58. Control specimens included cervical intraepithelial neoplasia (CIN) III lesions, squamous cell carcinomas (SCCs) of the cervix and lung, and colonic adenocarcinomas. Measures to minimise cross-contamination were implemented. RESULTS: The screening test followed by HPV DNA sequencing had the highest sensitivity. By this test HR HPV DNA was detected in 11 of 11 (100%) cervical intraepithelial neoplasia (CIN III) lesions, nine of 10 (90%) cervical SCCs, none of 10 (0%) colorectal adenocarcinomas and none of 10 (0%) SCCs of the lung. Thirty-nine (78%) endocervical adenocarcinomas contained HR HPV DNA, compared to one (2.0%) endometrial adenocarcinoma. CONCLUSIONS: The results suggest that HPV DNA testing could be a useful adjunct in distinguishing between endocervical and endometrial adenocarcinomas in curettings or small biopsy specimens.     

Human papillomavirus localization in cervical adenocarcinoma and adenosquamous carcinoma using in situ polymerase chain reaction: review of the literature of human papillomavirus detection in these carcinomas

Many studies have suggested that human papillomavirus (HPV) infection plays an important role in the carcinogenesis of the cervical adenocarcinoma. However, the prevalence of HPV infection in cervical adenocarcinoma and adenosquamous carcinoma varies among the studies. Cervical adenocarcinoma (24 cases) and adenosquamous carcinoma (16 cases), including the underlying non-neoplastic epithelium were examined for HPV-DNA using in situ polymerase chain reaction (PCR), which enabled visualization of the localization on a glass slide. In adenocarcinoma, HPV-DNA was found in 13 cases (54%) and in eight cases in underlying non-neoplastic epithelium, resulting in a total of 21 positive cases (88%). In adenosquamous carcinoma, HPV-DNA was detected in 12 cases (75%) and and the HPV-DNA localization of each component was pure adenocarcinoma, 28.6%; mixed, 54.5%; and pure squamous cell carcinoma, 83.3%. In the underlying non-neoplastic epithelium, HPV-DNA was found more frequently in the squamous epithelium (73.3%) than the cervical glands (6.3%). In conclusion, HPV-DNA was detected in 54% of adenocarcinoma, and the rate was elevated by HPV localization in the underlying non-neoplastic epithelium. HPV infection in the underlying squamous epithelium might be related to the carcinogenesis, even in cervical adenocarcinoma. HPV-DNA localization was different in each component of adenosquamous carcinoma.     

In situ hybridization for human papillomavirus DNA in uterine adenosquamous carcinoma with glassy cell features ("glassy cell carcinoma").

Eighteen uterine adenosquamous carcinomas that showed focal glassy cell features (33% to 85% of tumor histology) or predominant glassy cell features (greater than 85% of tumor histology) were studied by in situ hybridization for human papillomavirus (HPV). Viral DNA was present in neoplastic cells in five cases: type 18 in four cases (two cervical adenosquamous carcinomas with predominant glassy cell features, two cervical adenosquamous carcinomas with focal glassy cell features) and type 16 in one case (cervical adenosquamous carcinoma with predominant glassy cell features). Positive intranuclear staining for HPV DNA was present within areas of squamous and glandular differentiation and within areas with glassy cell features. The mean age of HPV(+) patients was less than HPV(-) patients (mean, 57 years, compared to 67 years). No significant association between HPV status and prognosis or glassy cell features was detected. Human papillomavirus types 16 and 18 are associated with adenosquamous carcinoma with predominant glassy cell features or focal glassy cell features, "glassy cell carcinoma." Automated colorimetric in situ hybridization is an effective method to detect HPV DNA.     

LOW GRADE DIFFUSE FIBRILLARY ASTROCYTOMA OF THE CEREBRAL HEMISPHERES: LONG TERM FOLLOW UP AND p53 MUTATION ANALYSIS

Introduction and aims: Distinguishing between adenocarcinomas of endocervical and endometrial origin histologically can be difficult, particularly in curetting specimens with minimal material for examination. Endocervical adenocarcinomas have been shown to contain HPV DNA of certain 'high risk' subtypes, whereas this has not been consistently demonstrated in endometrial adenocarcinomas. The aims of this study were to look at whether HPV DNA typing could aid in this differential diagnosis.
Methods: The study investigated the frequency of HPV DNA in paraffin embedded tissue samples from endocervical and endometrial adenocarcinoma specimens using PCR amplification techniques designed to detect HPV DNA including high risk subtypes 16, 18, 31, 33, 45 and 58. Cases were selected from PathCentre and King Edward Memorial Hospital files, mainly curetting specimens with subsequent definitive hysterectomy. All cases were reviewed by a gynaecological pathologist. Control specimens included CIN III lesions, squamous cell carcinomas (SCC's) of the cervix and lung, and colonic adenocarcinomas. Measures to prevent cross contamination were implemented.
Results: HPV DNA was detected in 11 of 11 (100%) CIN III lesions, 9 of 10 (90%) cervical SCC's, 0 of 100 (0%) colorectal adenocarcinomas and 1 of 10 (10%) SCC's of the lung. 26 of 34 (76.5%) endocervical adenocarcinomas contain HPV DNA with 20 (55.6%) containing high risk subtypes, compared to 2 of 29 (6.9%) endometrial carcinomas, one with high risk subtype.
Conclusions: Preliminary results suggest HPV DNA typing could be a useful adjunct in distinguishing between endocervical and endometrial adenocarcinomas on curetting specimens, and possibly in the diagnosis of metastatic carcinomas of the cervix.     

BCL10 as a useful marker for pancreatic acinar cell carcinoma,especially using endoscopic ultrasound cytology specimens

Acinar cell carcinomas (ACCs) of the pancreas are characterized by the histological and immunohistochemical features of acinar cell differentiation. Recently, BCL10, originally identified as a recurrent t(1;14)(p22;q32) translocation in MALT B‐cell lymphoma, was found to be immunohistochemically positive in some solid tumors, including ACC. To evaluate its diagnostic efficacy, we performed BCL10 immunohistochemistry and evaluated molecular markers correlated to pancreatic tumor lineages (neuroendocrine markers and a mutation analysis of KRAS and GNAS) using samples from 126 pancreatic tumors (17 ACCs, 24 pancreatic ductal adenocarcinomas, 4 adenosquamous carcinomas, 9 intraductal papillary mucinous neoplasms, 10 mucinous cystic neoplasms, 44 neuroendocrine tumors, 9 serous cystic tumors and 10 solid‐pseudopapillary neoplasms). BCL10 was exclusively expressed in normal acini. In pancreatic tumors, 14 of 17 (82%) ACCs and 2 of 4 (50%) adenosquamous carcinomas were positive, while the other subtypes were almost negative. We subsequently examined the diagnostic utility of BCL10 in endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) specimens using 57 pancreatic tumors. BLC10 correctly identified ACCs (9/13) and adenosquamous carcinomas (2/4) but none of the other subtypes (n = 41). Therefore, we suggested that BCL10 expression is a useful marker for acinar cell differentiation, particularly in the diagnosis of EUS‐FNA specimens.     

Carcinoma of the lung in Okinawa, Japan: With special reference to squamous cell carcinoma and squamous metaplasia

In Okinawa, a subtroplcal Island In southern Japan, squamous cell Carcinoma (SCC), especially the well-differentiated form, Is prevalent, while this form is relatively rare in both the mainland and other countries (e.g. United States of America). More patlents with SCC from Okinawa, moreover, were positive for human papillomavlrus (HPV) DNA by polymerase chain reaction (PCR) (79%), and harbored HPV types 6, 16 and 18, In combination. On the other hand, less than 30% of the mainland patlents were positive for HPV DNA by PCR. Those patients who were positive all harbored only one HPV type. Furthermore, in Okinawa, there were a signiflcant number of cases with adenosquamous carcinoma, and they too were positive for HPV DNA. The SCC and the adenocarcinoma cells adjacent to the SCC component In these cases were also positive for HPV DNA, and such adenocarcinoma cells were enlarged In size with relatively wide cytoplasm. The authors postulate that HPV infects adenocarcinoma cells and changes them to enlarged cells, followed by squamous metaplasla. In this report, HPV DNA was transfected to adenocarclnoma cells (cultured cell fines) and this showed that HPV causes squamous metaplasla. In addition, aberrant expression of p53 was demonstrated In a large number of the SCC cases In Okinawa. The enlarged adenocarclnoma cells adiacent to the SCC components In adenosquamous carcinomas also showed aberrant expression of p53.The recent advances In the studies of anti-oncogenes, p53, etc. and oncogenes are outlined. It Is to be noted that the molecular mechanisms of carcinogenesis in the lung have been studied In general, classifying lung tumors Into two groups, namely, small cell carcinoma (SCLC) and non-small cell carcinoma (NSCLC). However, because human lung cancer is represented by a wide variety of histological types, molecular genetic studies according to a more detailed histological subclasslflcatlon is needed.     

Distinct molecular features of colorectal carcinoma with signet ring cell component and colorectal carcinoma with mucinous component.

Signet ring cell carcinoma and mucinous carcinoma are distinct subtypes of colorectal adenocarcinoma. The morphologic and molecular spectra of colorectal carcinomas with various signet ring cell components and colorectal carcinomas with various mucinous components, compared to non-mucinous adenocarcinomas, have not been examined. The study groups consisted of 39 carcinomas with various signet ring cell components ('the signet group'), 167 carcinomas with various mucinous components ('the mucinous group'), and 457 nonmucinous adenocarcinoma. We visually estimated the amounts of signet ring cell and mucinous components in tumors, and subclassified the signet and mucinous groups according to the amount of each component (< or = 19, 20-49, and > or = 50%). We sequenced BRAF and KRAS, analyzed for microsatellite instability (MSI) and 18q loss of heterozygosity (LOH), and performed immunohistochemistry for TP53, cyclooxygenase-2 (COX2), MLH1, O-6-methylguanine DNA methyltransferase (MGMT), p16 (CDKN2A), and fatty acid synthase (FASN). Signet ring cell carcinoma (> or = 50% signet ring cell tumors) and < or = 49% signet ring cell tumors showed similar molecular features. Except for MSI and MGMT, > or = 50% mucinous tumors and < or = 49% mucinous tumors also showed similar molecular features. BRAF mutations, MSI, and MLH1 loss were more frequent in both the signet and mucinous groups than nonmucinous carcinoma. More frequent KRAS mutations and less frequent p16 loss and TP53 positivity were observed in the mucinous group than nonmucinous carcinoma. 18q LOH and COX2 overexpression were less common in the signet group than nonmucinous carcinoma. FASN levels were highest in the mucinous group, followed by nonmucinous carcinoma, and lowest in the signet group. In conclusion, a minor (< or = 49%) signet ring cell or mucinous component in colorectal carcinoma suggests molecular features similar to > or = 50% signet ring cell or mucinous carcinoma, respectively. Signet ring cell carcinoma and mucinous carcinoma are related subtypes of colorectal adenocarcinoma, but have molecular features distinct from each other.     

Human papillomavirus DNA in adenosquamous carcinoma of the lung

AIM: To investigate the presence of human papillomavirus (HPV) DNA in adenosquamous carcinoma of the lung--which is relatively common in Okinawa but not in mainland Japan--and examine its histological features. METHODS: Of 207 cases where primary lung cancers were surgically removed between January 1995 and June 1997 in Okinawa, 23 were adenosquamous carcinoma. HPV was detected by non-isotopic in situ hybridisation (NISH) and polymerase chain reaction (PCR) amplification with primers specific for E6 and E7 regions of the HPV genome. PCR products were analysed by Southern blotting. Immunohistochemical determination of high molecular weight cytokeratin (HMC) and involucrin was also carried out. RESULTS: 18 cases were positive for HPV DNA by PCR and NISH. HPV types 6, 11, 16, and 18 were found. Seven cases were dual positive for different types of HPV. Using NISH, HPV was also found in the squamous cell components and in neighbouring enlarged adenocarcinoma cells. The HMC and involucrin were demonstrated immunohistochemically in the same areas. CONCLUSIONS: HPV DNA was found in a high proportion (78.3%) of adenosquamous carcinomas in Okinawa, a region where HPV has previously been shown to be prevalent in squamous cell carcinoma of the lung. The adenocarcinoma cells adjacent to the squamous cell carcinoma component were enlarged and positive for HPV, HMC, and involucrin. This is thought to indicate the transition from adenocarcinoma to squamous cell carcinoma.     

Integration of human papillomavirus types 16 and 18 in cervical adenocarcinoma.

AIMS: To determine which type of human papillomavirus (HPV) is associated with cervical adenocarcinoma and whether the virus was integrated or episomal in two continents. METHODS: Biopsy specimens from the UK (n = 16) and South Africa (n = 22) were analysed by non-isotopic in situ hybridisation (NISH) for HPV types 6, 11, 16, 18, 31, 33, and 35 on archival biopsy specimens using digoxigenin labelled probes. RESULTS: A total of 20 adenocarcinomas (53%) from both groups contained HPV DNA. In the UK group, seven and four cases contained HPV 18 (44%) and 16 (25%) respectively. In the South African group, nine cases contained HPV 18 (41%) while HPV DNA was not detectable in the other 13 cases. Hence HPV 18 was present in 80% of HPV positive adenocarcinomas. CONCLUSIONS: The HPV 16 or 18 genome was integrated in all viral positive cases. In two cases HPV 18 was also present in an episomal form. These data indicate that HPV integration is common to cervical adenocarcinoma in two continents by the same methodology. The lower prevalence of HPV 18 detection in the South African group may have been due to the presence of other or unsequenced HPV types.     

p16 Immunoreactivity in unusual types of cervical adenocarcinoma does not reflect human papillomavirus infection

Houghton O, Jamison J, Wilson R, Carson J & McCluggage W G
(2010) Histopathology 57, 342–350
p16 Immunoreactivity in unusual types of cervical adenocarcinoma does not reflect human papillomavirus infection Aims: The association between human papillomavirus (HPV) and cervical carcinoma is well known, with HPV being identifiable in almost all cervical squamous carcinomas and most adenocarcinomas. However, the prevalence of HPV in unusual morphological types of cervical adenocarcinoma has not been investigated extensively. The aim was to determine HPV status in a series of primary cervical adenocarcinomas, enriched for unusual morphological types. The relationship between HPV and p16 immunoreactivity in these neoplasms was also investigated, as it is generally assumed that in cervical neoplasms diffuse p16 expression is predictive of the presence of high‐risk HPV. Methods and results: Sixty‐three cervical adenocarcinomas, comprising those of usual type (n = 43), minimal deviation type (n = 4), gastric type (n = 3), intestinal type (n = 3), mesonephric type (n = 3), clear cell type (n = 4), serous type (n = 2) and hepatoid type (n = 1) underwent linear array HPV genotyping and immunohistochemistry for p16. Overall, HPV was identified in 32 of 56 cases (57%) in which sufficient DNA was present for analysis. The most common HPV types were 16 and 18, with these being identified in 20 and 18 cases, respectively, either alone or in combination. Seventy‐eight per cent of usual‐type adenocarcinomas were HPV‐positive, as was the single serous carcinoma in which there was sufficient DNA for analysis. In contrast, all minimal deviation adenocarcinomas and those of gastric, intestinal, mesonephric and clear cell types were HPV‐negative, as was the single hepatoid carcinoma. All usual‐type adenocarcinomas exhibited p16 immunoreactivity (diffuse staining in all but one case), as did 11 of 20 of those of unusual morphological type (five focal, six diffuse). Conclusions: Most, but not all, cervical adenocarcinomas of usual type contain HPV, but those of unusual morphological type are almost always HPV‐negative. This has implications for the efficacy of HPV vaccination in the prevention of cervical adenocarcinoma. A significant proportion of cervical adenocarcinomas are p16‐positive in the absence of HPV, illustrating that in these neoplasms diffuse p16 immunoreactivity is not a reliable surrogate marker of the presence of high‐risk HPV.     

卵巢癌中k-ras 基因点突变及p53蛋白表达

目的 探讨k—ras基因点突变和p53蛋白表达在卵巢癌发生中的作用及致癌机制。方法 采用显微切割技术、半巢式PCR—RFLP技术和免疫组化染色检测55例卵巢癌及其交界性病变中的k—ras基因点突变和p53蛋白表达。结果 k-ras基因点突变率在黏液性腺癌(61．9％)明显高于浆液性腺癌(14．2％),在黏液性交界性腺瘤(61．5％)明显高于浆液性交界性腺瘤(12．5％)。p53蛋白表达率在浆液性腺癌(80％)明显高于黏液性腺癌(52％),并随组织学分级而增高。结论 黏液性腺癌主要通过腺瘤-交界性腺瘤-腺癌途径致癌,k—ms基因点突变是黏液性腺癌的早期事件,黏液性交界性腺瘤是黏液性腺癌的癌前病变。浆液性腺癌主要通过生发上皮直接恶性转化形成,p53蛋白表达在浆液性腺癌的发生中起重要作用,是浆液性腺癌的晚期事件。