her2+ breast cancer tied to disturbed circadian gene expression
 

1: Virchows Arch. 2009 Mar 19. [Epub ahead of print]

Disturbance of circadian gene expression in breast cancer.

Kuo SJ, Chen ST, Yeh KT, Hou MF, Chang YS, Hsu NC, Chang JG.
Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
To explore the mechanism of the disruption of circadian rhythm in breast cancer, we examined the expression of nine circadian genes in 53 newly diagnosed breast cancers by immunohistochemical staining, mutational analysis, and methylation analysis of the promoter of circadian genes. Our results showed that 37 of the 53 breast cancer tissues had hypermethylation on the promoters of PER1, PER2, CRY1, or BMAL1. Twenty-five out of 53 paired noncancerous (normal) tissues had methylation on the promoter of PER1 or CRY1. Our results indicated a higher frequency of concurrent methylation of PER1 and CRY1 promoters in cancerous and normal tissues. Promoter methylation of the PER1 correlates with c-erbB2 immunohistochemical reaction of >/=2+ (p = 0.012) and has a strong inverse correlation with estrogen receptor positivity (p = 0.016). We further analyzed the patterns of circadian gene expression by immunohistochemical methods and found that homogeneous expression of PER2 or BMAL1 is significantly associated with lymph node metastasis and poor prognosis. PER2 heterogeneous expression correlates with <2+ c-erbB2 immunohistochemical reaction. Heterogeneous expression of CLOCK is associated significantly with 3-year survival. In conclusion, the expression pattern of circadian genes might be a biomarker for the prognosis of breast cancer.
PMID: 19296127

is that why I have always had insomnia??

Dear Lani -
Once again you have posted something that I am sure NONE of us here ever thought of!!

This interests me:

"PER2 heterogeneous expression correlates with <2+ c-erbB2 immunohistochemical reaction. Heterogeneous expression of CLOCK is associated significantly with 3-year survival. In conclusion, the expression pattern of circadian genes might be a biomarker for the prognosis of breast cancer."

In lay terms, does this mean that LESS than 2+ overexpression is the marker? Wonder about those of who are 3+++ - or highly HER2 positive?

A little puzzling ...

Does this mean that my life as an unabashed night owl has served me wrong? Uh oh.

If you figure that cancer takes 10 years to grow before a tumor is visible, that would make sense for me. I worked in a startup where we worked till all hours in the early morning.

I was on a Melatonin trial; I wonder what the results will be, specifically for HER2+ people.

Steph N
 

I think you got a bit confused -- as they found that:
HOMOGENOUS expression of PER2 or BMAL1 is significantly associated with lymph node metastasis and poor prognosis....It was PER2 HETEROGENOUS expression correlates with <2+ c-erbB2 immunohistochemical reaction. Heterogeneous expression of CLOCK is associated significantly with 3-year survival.

I think they mean HOMOGENOUS PER2 which was assoctd with poor prognosis

HETEROGENOUS expression of PER2 seemed to be correlated with NON smplfied her2 expression or nonexpression and in contradistinction a better prognosis, unless one was hetergenous for PER but homogenous for BMALI in which case one's prognosis would be poor and one would be more likely to have more involved lymph nodes

I would have to go back to the original article ( I am travelling at the moment) to see if their comment on
eterogeneous expression of CLOCK is associated significantly with 3-year survival (means is associated significantly with GOOD vs POOR 3 year survival and how that correlated with her2


The sentence you didn't comment on also had import for her2+s:
As Drs. Pegram and Slamon say her2 amplification is associated with a downregulation of ER --so the other sentence you did not quote, went right along with that:
Promoter methylation of the PER1 correlates with c-erbB2 immunohistochemical reaction of >/=2+ (p = 0.012) and has a strong inverse correlation with estrogen receptor positivity (p = 0.016).

Hope this clarifies things a bit!