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[Evolution of cervical intraepithelial neoplasia]

Pfleiderer A

Gynakologe, 1981 Dec;14(4):194-8.
PMID: 7033078
Matched MeSH terms: Carcinoma in Situ/etiology; Carcinoma in Situ/epidemiology; Carcinoma in Situ/pathology*
Analysis and outcome of 502 cases of laser excision cone (LEC) at the Samaritan Hospital for Women, London

Yahya AA, McIndoe GA, Mason WP

Asia Oceania J Obstet Gynaecol, 1992 Dec;18(4):315-8.
PMID: 1492803

When performed based on cytology, histological accuracy of the laser cone specimen improved with the more severe cytology. The incidence of adenocarcinoma in situ is 1.0%. With and without residual disease, the rate of abnormal cytology after laser excision cone are 0.6% and 1.6% respectively. There is good correlation between colposcopic biopsy and cone specimen in the more severe lesions. Out of 139 cases of incomplete excision, only 3 cases had abnormal cytology at follow-up. The complication rates are very low.

Matched MeSH terms: Carcinoma in Situ/pathology; Carcinoma in Situ/surgery*
Fulltext Different altered stage correlative expression of high abundance acute-phase proteins in sera of patients with epithelial ovarian carcinoma

Chen Y, Lim BK, Hashim OH

J Hematol Oncol, 2009;2:37.
PMID: 19709441 DOI: 10.1186/1756-8722-2-37

The general enhanced expression of alpha1-antichymotrypsin (ACT), clusterin (CLU), alpha1-antitrypsin (AAT), haptoglobin beta-chain (HAP), and leucine rich glycoprotein (LRG) in the sera of patients with epithelial ovarian carcinoma (EOCa) was recently reported. In the present study, we compared the expression of the serum acute-phase proteins (APPs) in the patients according to their stages of cancer.

Matched MeSH terms: Carcinoma in Situ/blood*; Carcinoma in Situ/diagnosis; Carcinoma in Situ/metabolism; Carcinoma in Situ/pathology
Fulltext P53 expression in invasive pancreatic adenocarcinoma and precursor lesions

Norfadzilah MY, Pailoor J, Retneswari M, Chinna K, Noor LM

Malays J Pathol, 2011 Dec;33(2):89-94.
PMID: 22299208 MyJurnal

Patients with pancreatic adenocarcinoma are known to have a high mortality rate. The 5-year survival rate still remains low even now compared to that of the 1960's despite new advances in management including surgery, chemotherapy, pathological classification and molecular diagnostic technologies. Precursors to invasive pancreatic adenocarcinoma have been identified in the last ten years that include mucinous cystic neoplasm, intraductal papillary mucinous neoplasm and pancreatic intraepithelial neoplasia. p53 protein accumulation in the nuclei is a common molecular event in most human neoplasms. Our objective is to investigate p53 expression in pancreatic adenocarcinoma and precursor lesions and their significance. The selected study material encompassed 31 invasive ductal adenocarcinoma, 15 mucinous cystic neoplasm and papillary mucinous neoplasm, and 27 cases of pancreatic intraepithelial neoplasia including grade 1, 2 and 3. Immunoscore was given for each case based on intensity of staining and percentage of cells positive and compared between precursor lesions and invasive adenocarcinoma. A score of 50 and above was considered significant. The results showed that p53 expression increased progressively and significantly with the grade of pancreatic intraepithelial neoplasia and adenocarcinoma (p-value < 0.001). These findings support the concept of multistep carcinogenesis in pancreatic adenocarcinoma and suggest that p53 inactivation occurs in the progression of precursors to pancreatic adenocarcinoma.

Matched MeSH terms: Carcinoma in Situ/metabolism*; Carcinoma in Situ/pathology
Squamous cell carcinoma related antigen in uterine cervical carcinoma

Cheah PL, Yap SF, Looi LM, Sivanesaratnam V

Malays J Pathol, 1991 Jun;13(1):37-41.
PMID: 1795560

Squamous cell carcinoma-related antigen (SCC-Ag), first described by Kato and Torigoe in 1977, has been cited by various workers as a serological marker for some epithelial neoplasms. The most well-studied is its association with carcinoma of the uterine cervix. In January 1989, we embarked on a prospective, multivariate study at the University Hospital, Kuala Lumpur to assess the usefulness of serologically assaying SCC-Ag (using the Abbott RIA diagnostic kit) in our patients with carcinoma of the uterine cervix. We were also interested to ascertain whether SCC-Ag is a 'general' marker for all histological types of cervical carcinoma or specific for squamous carcinoma. From the time of commencement to June 1990, 35 newly-diagnosed and histologically-proven cases were entered into the study. Of these, 4 were keratinising squamous carcinoma, 18 large cell non-keratinising carcinoma, 3 adenosquamous carcinoma, 7 adenocarcinoma and 3 carcinoma-in-situ. Our preliminary results show that all keratinising squamous carcinoma and 1/3 each of large cell non-keratinising carcinoma, adenosquamous carcinoma and carcinoma-in-situ had positive pre-therapy serum SCC-Ag levels (i.e greater than 2 ng/ml, 2 ng/ml being an arbitrarily selected 'cut-off' value). In contrast, no adenocarcinoma was serologically positive. In addition, keratinising squamous carcinoma had the highest mean pre-therapy serum SCC-Ag level. The results imply that serum SCC-Ag is related to the (1) presence of squamous and not glandular differentiation and (2) degree of squamous differentiation.

Matched MeSH terms: Carcinoma in Situ/immunology*
The early detection of unsuspected carcinoma of cervix in Malaysia by exfoliative cytological screening

Sinnathuray TA, Lau KS

Med J Malaysia, 1973 Dec;28(2):70-4.
PMID: 4276263
Matched MeSH terms: Carcinoma in Situ/diagnosis*
Epidemiology of cervical carcinoma in Brunei Darussalam. Analysis of data on 27,208 women screened with cytologic examinations

Affandi MZ, Dun T, Mantuano V, Sidhu R, Lumplugh C, Telisinghe PU

Acta Cytol., 1993 Mar-Apr;37(2):175-80.
PMID: 8465637

During the five-year period from January 1985 to December 1989 a total of 27,208 women, representing 44.0% of the total female population over age 15 years in Brunei Darussalam, underwent a cytologic examination. The majority of them were Malays (62.32%), followed by Chinese (22.23%), while the remainder were the expatriate population living in the country. High grade squamous intraepithelial lesion (moderate dysplasia) was detected in 88 women (3.3/1,000), high grade squamous intraepithelial lesion (carcinoma in situ) was seen in 32 women (1.22/1,000), and invasive carcinoma was found in 43 women (1.37/1,000). The overall detection rate for cervical cancer was 2.79/1,000 women in the population screened. In Brunei Darussalam Malay women marry at an early age, 44% by the age of 19 years, leading to sexual contact before the age of 20. However, the incidence of cervical cancer is low among them. This could be because they belong to the Orthodox Muslim Society, in which promiscuity is not permitted. Hence, multiple sex partners could be an important factor in the etiology of cervical cancer, confirming the current trend of thought that cervical cancer is a sexually transmitted disease. A comparison of the epidemiologic risk factors among the various races living in Brunei Darussalam is made.

Matched MeSH terms: Carcinoma in Situ/epidemiology*; Carcinoma in Situ/pathology
Fulltext Expression of P16 in high-risk human papillomavirus related lesions of the uterine cervix in a government hospital, Malaysia

Krishnappa P, Mohamad IB, Lin YJ, Barua A

Diagn Pathol, 2014;9:202.
PMID: 25361681 DOI: 10.1186/s13000-014-0202-z

Cervical cancer is one of the most common cancers affecting women worldwide. It is well established that human papilloma virus (HPV) infection is the prime risk factor in the development of cervical cancer. The current screening and diagnostic tests have limitations in identifying the range of lesions caused by HPV. The current study aims to evaluate the diagnostic value of p16 immunohistochemical (IHC) investigation in high-risk human papillomavirus (HR-HPV) related lesions of the uterine cervix in Hospital Tuanku Jaafar, Seremban, Malaysia.

Matched MeSH terms: Carcinoma in Situ/diagnosis; Carcinoma in Situ/metabolism; Carcinoma in Situ/virology
Fulltext An immunohistochemical study of p53 in oral epithelium dysplasia and squamous cell carcinoma

Ma, M.S.

Malaysian Dental Journal, 2007;28(2):78-82.
MyJurnal

Squamous cell carcinoma (SCC) is the commonest cancer in the mouth. Multiple risk factors, such as smoking, alcohol consumption, irradiation, viruses infection and chronic irritation are thought to be responsible for the formation of oral squamous cell carcinoma. Although SCC can develop through a series of precancerous stages manifested as various degrees of epithelial dysplasia, this is not always the case. p53 is the commonest mutated gene in human cancers. Mis-sense mutation of the gene or complexing of the protein with viral or cellular proteins prolongs its half-life and leads to its detection by immunohistochemistry. This study was designed with the aim of demonstrating any possible relationship between p53 and oral squamous cell carcinoma by immunohistochemical staining techniques. A total of 66 specimens from the oral cavity (10 normal mucosa, 11 hyperkeratosis without dysplasia, 11 mild dysplasia, 11 moderate dysplasia, 10 severe dysplasia and 13 SCC) were examined for the presence of p53. The results show p53 was not expressed in normal mucosa, but was found with increasing frequency in increasingly severe dysplasia and SCC. In conclusion, this study shows p53 mutation is common in oral squamous cell carcinoma and probably occurs early in the multisteps of oral carcinogenesis.

Matched MeSH terms: Carcinoma in Situ
Systematic Review and Meta-Analysis on the Impact of Hexaminolevulinate- Versus White-Light Guided Transurethral Bladder Tumor Resection on Progression in Non-Muscle Invasive Bladder Cancer

Gakis G, Fahmy O

Bladder Cancer, 2016 Jul 27;2(3):293-300.
PMID: 27500197

Introduction: Although there is evidence that hexaminolevulinate (HAL)-based transurethral bladder tumor resection (TURBT) improves the detection of Ta-T1 non-muscle-invasive bladder cancer (NMIBC) as well as carcinoma in situ there is uncertainty about its beneficial effects on progression. Material and Methods: A systematic literature search was conducted according to the PRISMA statement to identify studies reporting on HAL- vs. white-light (WL-) based TUR-BT in non-muscle invasive bladder cancer between 2000 and 2016. A two-stage selection process was utilized to determine eligible studies. Of a total of 294 studies, 5 (4 randomized and one retrospective) were considered for final analysis. The primary objective was the rate of progression. Results: The median follow-up for patients treated with HAL- and WL-TURBT was 27.6 (1-55.1) and 28.9 (1-53) months, respectively. Of a total of 1301 patients, 644 underwent HAL- and 657 WL-based TURBT. Progression was reported in 44 of 644 patients (6.8%) with HAL- and 70 of 657 patients (10.7%) with WL-TURBT, respectively (median odds ratio: 1.64, 1.10-2.45 for HAL vs. WL; p = 0.01). Data on progression-free survival was reported in a single study with a trend towards improved survival for patients treated with HAL-TURBT (p = 0.05). Conclusions: In this meta-analysis the rate of progression was significantly lower in patients treated with HAL- vs. WL-based TURBT. These results support the initiation of randomized trials on HAL with progression as primary endpoint.

Matched MeSH terms: Carcinoma in Situ
Fulltext Bacillus Calmette-Guerin and bladder cancer

Razack AH

Asian J Surg, 2007 Oct;30(4):302-9.
PMID: 17962138 DOI: 10.1016/S1015-9584(08)60045-7

Bladder cancer is the second most common cancer of the urinary tract, and overall it is among the top 10 cancers in men. Transitional cell carcinoma (TCC) is the most common type, with the majority being superficial disease, i.e. the tumour has not gone beyond the lamina propria. The main problem with superficial TCC is the high recurrence rate. Various forms of treatment methods have been attempted to reduce the recurrence rate, with intravesical bacillus Calmette-Guerin (BCG) being the most successful to date. In fact, intravesical BCG is one of the most successful forms of immunotherapy in the treatment of any form of cancer. This article is a general review of BCG in bladder cancer with an emphasis on the indication and mechanism of action in reducing recurrence and progression.

Matched MeSH terms: Carcinoma in Situ/drug therapy
Fulltext Skin cancer caused by chronic arsenical poisoning--a report of three cases

Jaafar R, Omar I, Jidon AJ, Wan-Khamizar BW, Siti-Aishah BM, Sharifah-Noor-Akmal SH

Med J Malaysia, 1993 Mar;48(1):86-92.
PMID: 8341178

The association of arsenical poisoning with the development of skin cancer is well-known. In Malaysia, arsenic has been shown to coexist with tin in tin-mining land. Our preliminary investigation has shown that the level of arsenic in well water from a tin-mining area is high. We report 3 patients with cutaneous lesions typical of chronic arsenical poisoning such as hyperpigmentation, keratoses and skin cancer. These patients have positive histories of previous domicility in tin-mining areas. We conclude that these patients developed chronic arsenical poisoning from drinking well water polluted with arsenic from the tin-mining soil.

Matched MeSH terms: Carcinoma in Situ/chemically induced
Fulltext Circulating prolactin and in situ breast cancer risk in the European EPIC cohort: a case-control study

Tikk K, Sookthai D, Fortner RT, Johnson T, Rinaldi S, Romieu I, et al.

Breast Cancer Res, 2015 Mar 31;17:49.
PMID: 25887963 DOI: 10.1186/s13058-015-0563-6

INTRODUCTION: The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention.
METHODS: We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects.
RESULTS: We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2=1.35 (95% CI 1.04-1.76), Ptrend=0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (Phet=0.98) or baseline HT use (Phet=0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (Ptrend=0.06 vs Ptrend=0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors<4 years compared to ≥4 years after blood donation (Ptrend=0.01 vs Ptrend=0.63; Phet=0.04) and among nulliparous women compared to parous women (Ptrend=0.03 vs Ptrend=0.15; Phet=0.07).
CONCLUSIONS: Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.

Matched MeSH terms: Carcinoma in Situ/blood*
Fulltext Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma

Pathmanathan R, Prasad U, Sadler R, Flynn K, Raab-Traub N

N Engl J Med, 1995 Sep 14;333(11):693-8.
PMID: 7637746 DOI: 10.1056/NEJM199509143331103

BACKGROUND: The Epstein-Barr virus (EBV) is consistently detected in patients with nasopharyngeal carcinoma. To determine whether EBV infection is an early, initiating event in the development of this malignant tumor, we screened nasopharyngeal-biopsy samples, most of which were archival, for preinvasive lesions, including dysplasia and carcinoma in situ. Preinvasive lesions were found in 11 samples, which were tested for the presence of EBV.
METHODS: EBV infection was detected with in situ hybridization for EBV-encoded RNAs (EBERs) and by immunohistochemical staining for latent membrane protein 1 (LMP-1). The larger samples were also tested for the EBV genome with the use of Southern blotting. The expression of specific EBV RNAs was determined by the amplification of complementary DNA with the polymerase chain reaction.
RESULTS: Evidence of EBV infection was detected in all 11 tissue samples with dysplasia or carcinoma in situ. EBERs were identified in all eight samples tested, and LMP-1 was detected in all six of the tested samples. Six of the seven samples tested for the EBV termini contained clonal EBV DNA: Transcription of the latent EBV gene products, EBV nuclear antigen 1, LMP-1, LMP-2A, and the BamHI-A fragment, was detected in most of the samples. Viral proteins characteristic of lytic lesions were not detected.
CONCLUSIONS: Preinvasive lesions of the nasopharynx are infected with EBV. The EBV DNA is clonal, indicating that the lesions represent a focal cellular growth that arose from a single EBV-infected cell and that EBV infection is an early, possibly initiating event in the development of nasopharyngeal carcinoma. Preinvasive lesions contain EBV RNAs that are characteristic of latent infection but not the viral proteins that are characteristic of lytic infection. The detection of the EBV-transforming gene, LMP-1, in all the neoplastic cells suggests that its expression is essential for preinvasive epithelial proliferations associated with nasopharyngeal carcinoma.

Matched MeSH terms: Carcinoma in Situ/chemistry; Carcinoma in Situ/virology
PAK5 mediates cell: cell adhesion integrity via interaction with E-cadherin in bladder cancer cells

Ismail AF, Oskay Halacli S, Babteen N, De Piano M, Martin TA, Jiang WG, et al.

Biochem. J., 2017 Mar 24;474(8):1333-1346.
PMID: 28232500 DOI: 10.1042/BCJ20160875

Urothelial bladder cancer is a major cause of morbidity and mortality worldwide, causing an estimated 150 000 deaths per year. Whilst non-muscle-invasive bladder tumours can be effectively treated, with high survival rates, many tumours recur, and some will progress to muscle-invasive disease with a much poorer long-term prognosis. Thus, there is a pressing need to understand the molecular transitions occurring within the progression of bladder cancer to an invasive disease. Tumour invasion is often associated with a down-regulation of E-cadherin expression concomitant with a suppression of cell:cell junctions, and decreased levels of E-cadherin expression have been reported in higher grade urothelial bladder tumours. We find that expression of E-cadherin in a panel of bladder cancer cell lines correlated with the presence of cell:cell junctions and the level of PAK5 expression. Interestingly, exogenous PAK5 has recently been described to be associated with cell:cell junctions and we now find that endogenous PAK5 is localised to cell junctions and interacts with an E-cadherin complex. Moreover, depletion of PAK5 expression significantly reduced junctional integrity. These data suggest a role for PAK5 in maintaining junctional stability and we find that, in both our own patient samples and a commercially available dataset, PAK5mRNA levels are reduced in human bladder cancer compared with normal controls. Taken together, the present study proposes that PAK5 expression levels could be used as a novel prognostic marker for bladder cancer progression.

Matched MeSH terms: Carcinoma in Situ/metabolism; Carcinoma in Situ/pathology

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