Familial And Hereditary Terminology

Families containing two or more first- and or second-degree relatives with EC are designated as showing familial cancer clustering. The term familial does not consider age of onset or extrauterine cancers, such as colorectal or ovarian cancer, which if found in combination with EC, are cardinal features of the Lynch syndrome (4). Subsets of familial EC, when pedigrees are more extensively studied, may, in fact, be found to be hereditary. Hereditary EC, in contrast, is a more precise term that...

Hpv Biology 21 Structure

The HPV genome is an 8 kbp circle of double-stranded, covalently closed, and his-tone bound DNA, which is maintained as an episome in infected cells during the productive virus life cycle. It encodes eight viral proteins across three frames (Fig. 1 see Color Plate 2, following p. 50) (18). The HPV genome is histone bound and surrounded by a 55-60 nm, nonenveloped icosahedral capsid (19) of T 7 symmetry, which contains the genetically unrelated major capsid protein L1 and the minor capsid...

Msi

Not yet recognized, and the usual mutations associated with MSI in hereditary EC are not found in the sporadic cancers (29,30). It is postulated that there may be epigenetic inacti-vation of MSH1 in sporadic cases, which might not be evident in the usual mutational screens used to query the functional integrity of MLH1 (10,30,31). The manner in which MSI influences cell function is extremely complex, and beyond the scope of this chapter. Suffice to say that secondary inactivation of the...

References

Intermediate trophoblast a distinctive form of trophoblast with specific morphological, biochemical and functional features. Placenta 1984 5 349-370. 2. Kurman RJ. The morphology, biology, and pathology of intermediate trophoblast a look back to the present. Hum Pathol 1991 22 847-855. 3. Haining RE, Cameron IT, van Papendorp C, et al. Epidermal growth factor in human endometrium proliferative effects in culture and immunocytochemical localization in normal and...

Viral Clearance Vs Oncogenic Progression

Although, epidemiological studies show that more than 80 of HPV infections are benign and cleared within 12-18 months (32), a fraction of infections persists and can Fig. 4 (Color Plate 5, following p. 50). Examples of abnormal cervical cytopathology. (A) LSIL A cluster of cells demonstrating the enlarged nuclei, hyperchromasia, smudgy chromatin pattern, even some koilocytosis (cytoplasmic clearing) typical of an LSIL lesion. (B) HSIL A cluster of cells with markedly enlarged nuclei,...

DNA Mismatch Repair Genes

HNPCC has been linked to multiple genetic mutations in the DNA mismatch repair (MMR) genes (134,135). One function of the MMR genes is to detect and correct mismatched nucleotides in DNA strands. Loss-of-function of these genes leads to error-prone DNA replication and microsatellite instability. Eventually, buildup of genetic replication errors in oncogenes and tumor suppressor genes leads to carcinogenesis. Indeed, Risinger et al. (136) detected microsatellite instability in 75 of endometrial...

Ca 125

As mentioned earlier, CA 125 has shown promise for early detection of ovarian cancer and detection of recurrence. The rate of decline of CA 125 during chemotherapy has also been shown to be a potential prognostic marker. Several reviews have been written on the topic (13,132) and interested readers are referred to these reviews for a detailed discussion. ERBB2 is a member of the epidermal growth factor receptor family of receptor tyrosine kinases. Activation of this receptor activates...

Lsil Triage

LSIL is a benign disease in young women. The higher rate of regression of LSIL in adolescents compared with adult women led to more reasonable guidelines (13). Conservative observation of LSIL by cytology rather than immediate referral to col-poscopy in adolescents and young women is now accepted. In the United States, it is recommended that a young woman with LSIL return in 6 months for repeat cytology. Any abnormality on repeat cytology leads to referral to colposcopy. However, in adolescents...

Chromosomal Alterations And Cervical Cancer

Although, cytogenetic studies on cervical cancer have identified a number of non-random karyotipic changes involving chromosomes 1, 3, 5, 17, and X, the search for the critical genetic changes has been hampered by technical difficulties, such as the karyotypic complexity of this tumor. The advent of comparative genomic hybridization has opened a novel means of characterizing genomic imbalances and to date several studies have identified 3q gain, which occurred at severe dysplasia carcinoma in...

Natural Histories Of Hpv Lsil And Hsil In Adolescents

For more than a decade, numerous studies have documented the transient nature of HPV infection in young women. Although, up to 50 of adolescents acquire HPV in adolescence approx 90 will clear the infection, (31-33) with 79-90 clearing it within 24 months. Certain HPV types, such as HPV 16, clear more slowly than other high- or low-risk types and new infections are constantly occurring. There is evidence that having multiple types of HPVs also slow clearance (34). Whether this reflects a global...

Adolescent Biological Vulnerability

Young age at first intercourse has long been associated with risk for invasive cancer. The risk of invasive cancer increases twofold in women who initiate sexual intercourse under the age of 18 years as compared with those initiating sexual intercourse after 19 years when controlling the number of lifetime sex partners (23). This finding suggests that there is a certain biological vulnerability of the cervix of young women to HPV infection. The adolescent cervix is structurally different from...

Etiology Human Papillomaviruses

Causality requires a judgment based on scientific evidence from human and experimental studies, as strict causality studies are often not appropriate in humans. Evidence linking certain human papillomavirus (HPV) genotypes to cervical carcinoma is extensive and compelling. More than two decades of research has led to the fulfillment of criteria, as proposed by Hill, to establish a causal link between high risk HPV infection and cervical cancer (Table 1). HPV DNA was first isolated from biopsies...

EIN A Comprehensive Model of a Precancerous Lesion

A broad foundation of molecular, histological, and clinical outcome data has established the entity of EIN as the biological precursor for endometrioid endometrial adenocarcinoma (29). EIN lesions are precancerous lesions with particular biological and histological features that confer a heightened risk for concurrent or future endometrioid endometrial cancer. EIN was defined through an open-ended discovery process, which correlated presence of those molecular features predicted in...

Info

In this ongoing phase III prophylactic vaccination trial of HPV16 L1 VLPs, women without evidence of HPV16 infection were vaccinated three times with HPV16 L1 VLPs or placebo and followed for new persistent HPV16 infection or development of CIN (11,67). aDuring the first 1.5 years after immunization, vaccination provided 100 (95 confidence interval 90-100 p < 0.0001) protection against acquisition of persistent HPV16 infection. Although, 41 incident persistent HPV16 infections and 9 HPV16 DNA...

Future Perspectives In Studying Ovarian Tumors

The tumorigenesis model described here provides a framework for future molecular and clinical studies of ovarian cancer (64). There are several research directions that need to be addressed in order to better understand the pathogenesis of ovarian carcinoma. The most critical include the introduction of new molecular genetic tools and population-based studies of ovarian serous borderline tumors. First, the key molecular events that are involved in the development of different subtypes of...

An Overview Of Endometrial Adenocarcinoma

Columnar Cell Cervical Cancer

Endometrial adenocarcinoma is the most common invasive malignant neoplasm of the female genital tract, with an estimated 40,000 diagnosed cases and 6600 deaths in 2002 in the United States 1 . Fortunately, surgery alone provides effective therapy for about 80 of these women, but very few of those with advanced or metastatic disease are cured by radiation, hormonal or chemotherapy. Significant future improvements in survival most likely will result from a better understanding of the pathways...

Type I And Type Ii Tumors Are Characterized By Unique Molecular Features

Braf And Kras Mutually Exclusive

Because serous carcinoma is the most common type of ovarian carcinoma, this discussion is focussed on low- and high-grade serous carcinomas as they represent the prototypes of type I and type II carcinomas, respectively. Both low- and high-grade serous carcinomas can be distinguished by unique molecular genetic alterations. Among Precursors and Molecular Genetic Alterations of Type I and Type II Tumors of the Ovary Type I tumors Precursorsa genetic alterations Malignant Brenner transitional...