Overexpression of Cyclooxygenase-2 (COX-2) Correlates with Grade, Stage and Lymph Node Status in Colorectal Adenocarcinoma (CRC)

KA Robstad, JD Choate, JS Ross, CE Sheehan and DM Jones, Department of Pathology, Albany Medical College, Albany, NY

Background: COX-2 is an inducible enzyme involved in prostaglandins metabolism that has been associated with cellular resistance to apoptosis both in normal and malignant epithelial cells.  Over-expression of COX-2 has been identified in various epithelial malignancies including colorectal CRC, but large scale studies of its prognostic significance for the disease have not been previously performed.

Design: Formalin-fixed, paraffin-embedded sections from 155 CRC were immunostained by an automated method (Ventana Medical Systems; Tucson, AZ) using mouse monoclonal COX-2 (clone CX-294, DAKO, Carpinteria, CA).  Cytoplasmic immunoreactivity was semi quantitatively evaluated based on both intensity (weak, moderate and intense) and distribution (focal <10%, regional 10 to 50% and diffuse >50%) and results were correlated with histologic and prognostic variables.

Result: Intense diffuse over-expression of COX2 was observed in 71/155 (46%) of CRC and correlated with increasing tumor grade [16% of grade 1 vs 51% of grade 2 vs 48% of grade 3, p=0.018); advanced AJCC stage (38% of stage I/II vs 53% of stage III/IV; p=0.048); and lymph node status (35% node negative vs 53% node positive, p=0.024).  COX2 over-expression did not correlate with disease recurrence or overall survival. On multivariate analysis, pathologic stage at diagnosis independently predicted patient survival.

Conclusion: Over-expression of COX-2 is associated with high tumor grade, advanced pathologic stage and positive lymph node status in CRC. Further study of COX-2 expression in CRC, particularly with reference to its clinical prognostic implications, appears warranted.

AMC Pathology Gives Back…

This past Monday, a group of folks from the Albany Medical Center Department of Pathology volunteered their time to assist in the preparation of Equinox Inc.’s 40th annual Thanksgiving Day Dinner.  The group consisted of an attending physician, two residents, a histologist (all of which were also Siena alumni as well), as well as an Albany-area social worker.  The group aided in the preparation and counting of donated food stuffs as well as in the cleaning up of the facilities. In the short days leading up to the big finale!

A word about Equinox  Inc.: 
Equinox provides assistance in a safe and supportive environment to individuals and families to help them find the resources within themselves to grow and to make positive and lasting changes in their lives and within their communities.

They also organize the largest Thanksgiving Day dinner program in the Capitol Region.  Approximately 500 meals will be served this year at a sit down dinner, and an additional 7,800 meals are prepared at the Empire State Plaza and then delivered by volunteers to individuals who live within a 40 mile radius of downtown Albany.  The recipe for the dinner includes 8,000 pounds of turkey, 2,000 pounds of ham, 2,800 pounds of yams, 940 pies, 625 dozen dinner rolls, 48 gallons of cider and 19,500 pieces of fruit.  All of the food and the vast majority of help is donation-based.

In addition to the donation of physical bodies to the cause, the department also raised enough money to donate 300lbs of turkeys, 100lbs of potatoes and 50lbs of carrots for the meal preparation.

…and people say Pathologists are antisocial!  tsk, tsk!

Next up for the department:
Adopt-A-Family Christmas Present Drive for Unity House!

 

Happy Holidays from the 1x Objective!

Multitouch Surface Used for Virtual Autopsy Table

Researchers at Sweden’s Norrköping Visualization Center  (link in Swedish) have developed a “virtual autopsy” experience using a multitouch surface computer and various patient images.  Using CT and MR imagery data procured posthumously, the program recreates the body in three-dimensional space with multiple layers than can be applied or removed with the swipe of a hand.

The utility of this non-invasive approach is, according to the team, multifactorial.  First, the perceivable educational benefits for teaching anatomy are obvious (although, can you really replace the cadaveric experience?).  Additionally, the system could be used by forensic pathologists.  They highlight that the whole process can be completed in minutes as opposed to the hour for a traditional autopsy and also that 3-D imagery would be more understandable and less “gruesome” for juries to see.

Watch the video below for more information and to watch how slick it is in action.

As of now, there is only one working prototype, but the group is planning on starting production in the near future.

It seems very intuitive and cool for sure; but as far as practicality is concerned, we all know there’s no substitute for the real thing…  Now, if only they could combine this with smell-o-vision for the real experience!

Gummy Worm Karyotype [Image Cache]

by artist Kevin Van Aelt.

I know my karyotype would have many delicious deletions…

Check out the rest of his portfolio here.  Some of his other works include such pieces as an EKG hairstyle, and a cookie with metaphase icing.

[Kevin Van Aelt via Serious Eats]

Bmi-1 Nuclear Overexpression Correlates with Low Tumor Grade and Lengthened Overall Survival in Colorectal Adenocarcinoma (CRC)

JD Choate, KA Robstad, CE Sheehan, JS Ross and DM Jones
Department of Pathology, Albany Medical College, Albany, NY

Bmi-1 Staining at 20x

Background: Bmi-1 protein expression plays a vital role in cell cycle regulation and senescence, and has been implicated in lymphangiogenesis and carcinogenesis.  Bmi-1 oncogene overexpression has been previously identified in several human malignancies including hematologic malignancies, as well as carcinomas including CRC; however, clinicopathologic and prognostic significance of Bmi-1 expression has not been fully elucidated.

Design: Formalin-fixed, paraffin-embedded sections from 153 colorectal adenocarcinomas (CRCs) were immunostained by an automated method (Ventana Medical Systems; Tucson, AZ) using mouse monoclonal Bmi-1 (clone F6; Millipore, Burlington, MA).  Nuclear and cytoplasmic immunoreactivity were semi quantitatively evaluated based on both intensity (weak, moderate and intense) and distribution (focal <10%, regional 10 to 50% and diffuse >50%) and results were correlated with clinic-pathologic variables.

Result: Bmi-1 nuclear immunoreactivity was over-expressed in 100/153 (65%) of CRC, while cytoplasmic over-expression was observed in 62/153 (41%). Nuclear overexpression correlated with low tumor grade (77% grade 1 vs 72% grade 2 vs 49% grade 3, p=0.016) and lengthened overall survival (80% alive vs 59% expired, p=0.008). There were no other significant correlations.  On multivariate analysis, only pathologic stage at diagnosis independently predicted patient survival.

Conclusion: Bmi-1 overexpression is associated with lower grade CRC’s and significantly correlates with increased overall survival. These findings indicate that Bmi-1 over-expression may be a significant prognostic biomarker that could play a role in the planning of therapy in CRC. Further study of Bmi-1 expression in CRC appears warranted.

Prognostic Implications of Cytoplasmic and Nuclear Overexpression of Lipocalin-2/NGAL in Colorectal Adenocarcinoma (CRC)

KA Robstad, JD Choate, CE Sheehan, JS Ross and DM Jones
Department of Pathology, Albany Medical College, Albany, NY

Lipocalin-2 Stain at 20x

Background:  The lipocalin family is a diverse group of secreted soluble proteins that bind hydrophobic ligands and act as small molecule transporters.  Lipocalin-2, also known as neutrophil gelatinase-associated lipocalin (NGAL), is an inflammatory cytokine upregulated in acute inflammatory conditions which has been found to be over-expressed in various human malignancies including carcinomas of the breast, ovary, pancreas and colon.  The prognostic significance of Lipocalin-2 expression in CRC has not been previously investigated.

Design: Formalin-fixed, paraffin-embedded sections from 156 colorectal adenocarcinomas (CRCs) were immunostained by an automated method (Ventana Medical Systems; Tucson, AZ) using rat monoclonal lipocalin-2/NGAL (R&D Systems, Minneapolis, MN).  Cytoplasmic and nuclear immunoreactivity was semi quantitatively evaluated based on both intensity (weak, moderate and intense) and distribution (focal <10%, regional 10 to 50% and diffuse >50%) and results were correlated with clinicopathologic variables.

Result: Lipocalin-2 immunoreactivity was predominately cytoplasmic, however, significant nuclear immunoreactivity was noted in a subset of cases.  Intense diffuse cytoplasmic overexpression of lipocalin-2 was observed in 30/156 (19%) of CRC and correlated with early AJCC stage (28% of stage I/II vs 11% of stage III/IV; p=0.007) and presence of concomitant Crohn’s disease (100% with Crohn’s vs 0% without Crohn’s).  Nuclear lipocalin-2 immunoreactivity was noted in 6 cases, all 6 of which (100%) were lymph node negative (p=0.005), early stage (p=0.015), and moderately differentiated/grade 2 (p=0.102) tumors.  Lipocalin-2 over-expression did not correlate with disease recurrence or overall survival. On multivariate analysis, pathologic stage at diagnosis independently predicted patient survival.

Conclusion: Cytoplasmic lipocalin-2 over-expression is associated with both early AJCC tumor stage as well as the presence of pre-existing Crohn’s disease potentially reflecting its role as an inflammatory cytokine.  Nuclear expression, only identified in a small subset of CR, was found to correlate significantly with low-stage, moderately differentiated, lymph node-negative tumors. Further studies of both nuclear and cytoplasmic lipocalin-2 expression in CRC appear warranted.

DIY Cell Phone Microscope

This past summer, various news sources reported on Cell Scope, the portable Cell Phone Microscope.  It was a well-developed and supported, sophisticated device that at least seemed like it could be very helpful in underserved areas for such applications as searching peripheral smears for malarial parasites. 

Well, if you just cannot wait for Cell Scope to come to market, or if you are on more of a shoe-string budget, researchers at UCLA have fabricated a cell phone microscope of their own, of the DIY variety.

The engineer behind this project, Aydogan Ozcan told the New York Times that the device was created out of $10 worth of off-the-shelf parts (based on the picture, it seems as if they have some pretty amazing shelves) and actually involves no lens!  Instead, the set-up uses the cell phone’s camera sensor to read light scatter created by shining an LED light through a blood sample (I believe, much like routine automated hemocytometry) and the rig then reports the acquired information wirelessly to a computer which is able to interpret the information and report out certain information about the sample from the white cell count to the presence of malarial parasites.

Not surprisingly, this kit set-up is also targeted at indigent and undeserved areas for basic blood interpretation including utilization in the diagnosis of malaria.  Again, no word on price or release date, or more importantly for the DIY-er: instructions; I’m still waiting…

[New York Times via Gizmodo]

Moving to a New Department!

The pathology department at Albany Medical Center is moving!  Our current building is being demolished and replaced by a new, second, huge OR suite on track for a 2011 opening.  Our new accommodations will now be in the hospital proper (very exciting).

We are moving Tuesday, but the bones are all in place, and the new dept. looks beautiful.  We will have two full sign out rooms accommodating 4 multi-headed scopes.  A single central residents room with 16 cubbies and a separate attached office for the chief residents.  Each of the cubbies has its own ethernet jack, and there is a common area for department computers, printers, and image capturing scopes.  The new conference room is greatly opened and expanded and will contain a new projection system with a smart board and all modular furniture.  We are giving up some window real estate, but ultimately we are closer to the morgue, the OR, the cafeteria and the parking garage; so, overall, I think this is definitely an upgrade for us.

How does it stack up to yours?

Check out me Qik’ed video walk-through below:

more about “The New AMC Path Dept.“, posted with vodpod

New York: Get a flu shot, or get fired.

I’m not sure if this kind of mandate has been rolled out across the country, but here in New York, we were told, up front, that the entire hospital staff was required to get a flu shot this year (and the swine flu shot as well when it comes out) OR face termination.  Fired over a flu shot?  I thought Cleveland Clinic’s anti-smoking policy was pushing it…

There have already been talks of protests and law suits here in Albany.  Personally, I’m indifferent, but I guess I can see their point- being forced into doing something they otherwise would not have done, but is it worth a law suit?  Probably not.

I’ve heard a few different explanations for dissent.  Perhaps the most interesting reasoning I’ve heard is this- because the flu shot is offered for free or reduced cost by the drug companies, the companies are protected from litigation if a patient is injured as a direct result of the vaccination.  Another question to be asked would be, “Does the punishment fit the crime?”  Is termination the proper penalty for not receiving a shot?  They require house staff to be up to date on their vaccinations, after all.  So is that any different?  I suppose.  Can you fire an employee for poor hygiene?  Either of my examples could perceivably place patients at risk, but it’s not clear to me that either of these would be enforced.  Finally, do ALL employees really need the shot, even those with no patient contact?  As a pathologist, I did ask myself that question.  Sure we have some patient contact, and we surely have contact with other employees that do have contact with patients, so I suppose the idea is to cover all your bases and just vaccinate everyone.

In the end, it seems clear to me that the New York State government has gotten swept up in the media craze surrounding the H1N1 virus, which, as a concept is sad, but in practice is probably better for everyone in the long run.  I do wonder, however, if we will be required to get our flu shots next year too…

Albany Medical Center’s CEO Defends the Public Option

Below is a link to the mp3 of an interview with Albany Medical Center’s CEO Jim Barba in which he defends Obama’s Public Option proposal.  The interview originally aired on Siena College’s WVCR Radio Station.

I thought it was a very interesting perspective, and is yet another health professional coming out in support of the public option.  Interesting!

He goes on to talk about the viability of a single-payer system as well (waters far too murky for me).

I guess when I’ve thought about health care reform, I had never really imagined that the CEO of a hospital would support a single-payer system…  A public option? Sure, but not single payer.  He does make an interesting argument, however.

Definitely worth a listen!

AMC CEO Supports Public Option