Diagnosed with Ovarian and uterine cancer both sage 1A

[scoob61]

I presented with a large complex ovarian cyst 14.5 x 12.5 x 8.0cms. I had a planned Total Hysterectomy my Pathology results showed Grade 1 A  cancer within the Cyst and a further  cancer  Grade 1 A an incidental finding within my uterus both seperate Primary tumours. I am only 46 Yrs old I now face examination of my Para-aortic Nodes within the next few weeks I wondered if anyone else has had Synchronous Cancers or Hereditary Nonpolyposis Colorectal Cancer diagnosed.

[Annekathryn Goodman, M.D.]

hi There,

Hereditary non polyposis colon cancer syndrome or HNPCC is family cancer syndrome where there are family members in each generation has one of the following cancers: colon, breast, uterine, and some others. I have pasted a nice summary below. There is a blood test available.

You are very lucky to have found early uterine and ovarian cancers!  You can talk to a genetic counselor about pursuing a genetic diagnosis. You should also get a colonoscopy and mammogram

best wishes


Disease name and synonyms
Colon cancer, nonpolyposis
HNPCC syndrome (hereditary nonpolyposis colorectal cancer)
Clinical definition
The diagnosis of HNPCC syndrome is based on the meeting of three criteria, defined in 1991 at Amsterdam by the International Study Consortium on HNPCC syndrome.
A number criterion (at least three family members have colon or rectal cancer);
A kinship criterion (2 generations of first-degree relatives are affected);
An age criterion (at least one of the cancers should occur before the age of 50 years).
Extracolonic manifestations of HNPCC syndrome consist of cancers of the endometrium (40%), excretory urinary tract, stomach, biliary tract (about 10%), small intestine (10%) and ovary (3%). Two syndromes have been recently included into HNPCC syndrome and predispose to either cutaneous tumors, keratoacanthoma type, spinocellular cancer and sebaceous cyst (Muir-Torre syndrome), or cerebral tumors, glioblastoma type (Turcot syndrome).
  
Disease course
In the families identified on the basis of these criteria, affected patients develop mainly colorectal cancers (CRC) and endometrial cancers, with cumulative risks of 90% and 40%, respectively. Prognosis is thus strongly influenced by the stage at diagnosis of these tumors.
Biennial screening colonoscopy is proposed to children of affected patients from the age of 25 years, or 5 years before the age at diagnosis of the earliest cancer in the family. Annual gynecological surveillance is necessary for women over 30 years and consists of an endovaginal echography that may be completed with transvaginal ultrasound biopsy.
  

Heredity
About 3 to 5% of CRC occur in patients carrying HNPCC syndrome, which is an autosomal dominant inherited disease.

Biochemical basis
Genes whose alteration is associated with HNPCC syndrome belong to a vast family of genes involved in DNA mismatch repair (MMR), i.e. in the control of fidelity for replication.
MMR system inactivation was found in tumor cells to result in genomic instability (called RER for replication error or MSI for microsatellite instability). RER+ phenotype is observed in more than 80% of HNPCC syndrome-associated CRC and in almost 10% of sporadic CRC. It is currently recommended to determine whether the tumor phenotype is RER+ before screening for MMR genes mutations when the Amsterdam criteria are not completely fulfilled.
  

Gene
Localization and identification
Five genes of which constitutional alteration is responsible for the occurrence of the disease have been identified;
4 genes belong to the same MMR gene family: hMLH1 on chromosome 3p21.3 and hMSH2 on chromosome 2p22-p21, which are involved preponderantly, hPMS2 on chromosome 7p22 and hMSH6 (or GTBP) on chromosome 2p16. The gene for TGFb type II receptor (TGFbRII) is the latest identified.

Mutations
At least half of the constitutional mutations associated with a HNPCC syndrome cause premature translational termination. Missense mutations are more difficult to interpret.

Diagnosis methods
Clinical methods
Clinical diagnosis of HNPCC syndrome is based on the number of familial and individual factors included in Amsterdam criteria.

Biochemical methods
No biochemical test is available to establish the diagnosis.

Genetic methods
The proportion of HNPCC syndromes associated with a constitutional mutation is estimated at 75% in HNPCC syndromes fulfilling strictly the Amsterdam criteria. In this clinical case, MSH2, MLH1 and MSH6 are involved in descending order of frequency, in 40%, 30% and 5% of the cases, respectively. Mutations affecting the other genes occur exceptionally. Genetic alteration is not identified in 25% of the cases. Prescreening methods for mutations in the coding sequence that do not rely on the predictable consequences at the protein level, are preferably used (DGGE, SSCP). These methods will first analyze the genes MLH1 (19 exons) and MSH2 (16 exons), then MSH6 (10 exons), and every electrophoretic variants will be sequenced.

Genetic counseling
Within a family, genetic counseling is based on the identification of a deleterious constitutional mutation in a clinically affected patient. A genetic test can be used to tailor the clinical surveillance of patients at risk only if the mutation is predicted to result in the synthesis of a truncated protein. Any possible genotype-phenotype correlation that have not been demonstrated cannot be taken into consideration.

Prenatal diagnosis
HNPCC syndrome is an adult disease. Cancers associated with HNPCC syndrome seem to have a low metastatic potential through the bloodstream. Surveillance methods of organs at high cancer risk are efficient. Surgical treatment of the organ in which cancer is discovered is curative.
  

Therapeutic perspectives
Therapeutic methods that are currently available aim to prevent the malignant complications of the disease. These methods are mainly surgical. No curative drug treatment is available.
  

[scoob61]

Can I thankyou for you response and guidance with regard to further investigations that will ensure I am not at risk of developing further cnacers. My Gynaecologist has organised Genetic Testing and Examination of the Colon once I have this Staging of the Para- Aortic nodes completed.
The Ovarian Cyst had caused Acute retention of urine I had to be catheterised as an Emergency it was then discovered  following pelvic examinations and  Ultrasound Scan.
My Gynacologist/Oncologist has reinforced to me these 2 cancers were a Incidental finding Ovarian cancer is rarely diagnosed at this very early stage. The finding of a second tumour in the uterus was a chance finding during Pathology my Gynacologist has said this is very rare to have two cancers develop I am aged 46 and had not had any problems with my periods they were regular with no symptoms of the menopause.
My Cyst was a Blessing in disguise a Guardian Angel !